Digitalization of patient-specific information over the past 2 decades has dramatically altered health care delivery. Nonetheless, this technology has yet to live up to its promise of improving patient outcomes, in part due to data storage challenges as well as the emphasis on data entry to support administrative and financial goals of the institution.^1-4 Substantially less emphasis has been placed on the retrieval of information required for accurate diagnosis.

A new search engine, Voogle, is now available through Microsoft Internet Explorer (Redmond, WA) to all providers in the US Department of Veterans Affairs (VA) on any intranet-enabled computer behind the VA firewall. Voogle facilitates rapid query-based search and retrieval of patient-specific data in the VA Corporate Data Warehouse (CDW).

Case Example

A veteran presented requesting consideration for implantation of a new device for obstructive sleep apnea. Guidelines for implantation of the new device specify a narrow therapeutic window, so determination of his apnea-hypopnea index (AHI) was critical. The patient had received care at more than 20 VA facilities and knew the approximate year the test had been performed at a non-VA facility.

A health care provider (HCP) using Voogle from his VA computer indexed all Veterans Information Systems and Technology Architecture (VistA) notes for the desired date range. The indexing of > 200 notes was completed in seconds. The HCP opened the indexed records with Voogle and entered a query for “sleep apnea,” which displayed multiple instances of the term within the patient record notes. A VA HCP had previously entered the data from the outside sleep study into a note shortly after the study.

This information was found immediately by sorting the indexed notes by date. The total time required by Voogle to find and display the critical information from the sleep study entered at a different VA more than a dozen years earlier was about 1 minute. These data provided the information needed for decision making at the time of the current patient encounter, without which repeat (and unnecessary) testing would have been required.

Information Overload

Electronic health records (EHRs) such as VistA, upload, store, collate, and present data in near real-time across multiple locations. Although the availability of these data can potentially reduce the risk of error due to missing critical information, its sheer volume limits its utility for point-of-care decision making. Much patient-specific text data found in clinical notes are recorded for administrative, financial, and business purposes rather than to support patient care decision making.^1-3 The majority of data documents processes of care rather than HCP observations, assessment of current status, or plans for care. Much of this text is inserted into templates, consists of imported structured data elements, and may contain repeated copy-and-paste free text.

Data uploaded to the CDW are aggregated from multiple hospitals, each with its own “instance” of VistA. Often the CDW contains thousands of text notes for a single patient. This volume of text may conceal critical historical information needed for patient care mixed with a plethora of duplicated or extraneous text entered to satisfy administrative requirements. The effects of information overload and poor system usability have been studied extensively in other disciplines, but this science has largely not been incorporated into EHR design.^1,3,4

A position paper published recently by the American College of Physicians notes that physician cognitive work is adversely impacted by the incorporation of nonclinical information into the EHR for use by other administrative and financial functions.²

Information Chaos

Beasley and colleagues noted that information in an EHR needed for optimal care may be unavailable, inadequate, scattered, conflicting, lost, or inaccurate, a condition they term information chaos.⁵ Smith and colleagues reported that decision making in 1 of 7 primary care visits was impaired by missing critical information. Surveyed HCPs estimated that 44% of patients with missing information may receive compromised care as a result, including delayed or erroneous diagnosis and increased costs due to duplication of diagnostic testing.⁶

Even when technically available, the usability of patient-specific data needed for accurate diagnosis is compromised if the HCP cannot find the information. In most systems data storage paradigms mirror database design rather than provider cognitive models. Ultimately, the design of current EHR interaction paradigms squanders precious cognitive resources and time, particularly during patient encounters, leaving little available for the cognitive tasks necessary for accurate diagnosis and treatment decisions.^1,3,4,7

VA Corporate Data Warehouse

VistA was implemented as a decentralized system with 130 instances, each of which is a freestanding EHR. However, as all systems share common data structures, the data can be combined from multiple instances when needed. The VA established a CDW more than 15 years ago in order to collate information from multiple sites to support operations as well as to seek new insights. The CDW currently updates nightly from all 130 EHR instances and is the only location in which patient information from all treating sites is combined. Voogle can access the CDW through the Veterans Informatics and Computing Infrastructure (VINCI), which is a mirror of the CDW databases and was established as a secure research environment.

The CDW contains information on 25 million veterans, with about 15 terabytes of text data. Approximately 4 billion data points, including 1 million text notes, are accrued nightly. The Integrated Control Number (ICN), a unique patient identifier, is assigned to each CDW record and is cross-indexed in the master patient index. All CDW data are tied to the ICN, facilitating access to and attribution of all patient data from all VA sites. Voogle relies on this identifier to build indexed files, or domains (which are document collections), of requested specific patient information to support its search algorithm.

Structured Data

Most of the data accrued in an EHR are structured data (such as laboratory test results and vital signs) and stored in a defined database framework. Voogle uses iFind (Intersystems Inc, Cambridge, MA) to index, count, and then search for requested information within structured data fields.

Unstructured Text

In contrast to structured data, text notes are stored as documents that are retrievable by patient, author, date, clinic, as well as numerous other fields. Unstructured (free) text notes are more information rich than either structured data or templated notes since their narrative format more closely parallels providers’ cognitive processes.^1,7 The value of the narrative becomes even more critical in understanding complex clinical scenarios with multiple interacting disease processes. Narratives emphasize important details, reducing cognitive overload by reducing the salience of detail the author deems to be less critical. Narrative notes simultaneously assure availability through the use of unstandardized language, often including specialty and disease-specific abbreviations.¹ Information needed for decision making in the illustrative case in this report was present only in HCP-entered free-text notes, as the structured data from which the free text was derived were not available.

Search

The introduction of search engines can be considered one of the major technologic disruptors of the 21st century.⁸ However, this advance has not yet made significant inroads into health care, despite advances in other domains. As of 2019, EHR users are still required to be familiar with the system’s data and menu structure in order to find needed information (or enter orders, code visits, or any of a number of tasks). Anecdotally, one of the authors (David Eibling) observed that the most common question from his trainees is “How do you . . .?” referring not to the care of the patient but rather to interaction with the EHR.

What is needed is a simple query-based application that finds the data on request. In addition to Voogle, other advances are being made in this arena such as the EMERSE, medical record search engine (project-emerse.org). Voogle was released to VA providers in 2017 and is available through the Internet Explorer browser on VA computers with VA intranet access. The goal of Voogle is to reduce HCP cognitive load by reducing the time and effort needed to seek relevant information for the care of a specific patient.

Natural Language Processing

Linguistic analysis of text seeking to understand its meaning constitutes a rapidly expanding field, with current heavy emphasis on the role of artificial intelligence and machine learning.¹ Advances in processing both structured data and free-text notes in the health care domain is in its infancy, despite the investment of considerable resources. Undoubtedly, advances in this arena will dramatically change provider cognitive work in the next decades.

VistA is coded in MUMPS (Massachusetts General Hospital Utility Multi-Programming System, also known as M), which has been in use for more than 50 years. Voogle employs iKnow, a novel natural language processing (NLP) application that resides in Caché (Intersystems, Boston, MA), the vendor-supported MUMPS infrastructure VistA uses to perform text analysis. iKnow does not attempt to interpret the meaning of text as do other common NLP applications, but instead relies on the expert user to interpret the meaning of the analyzed text. iKnow initially divides sentences into relations (usually verbs) and concepts, and then generates an index of these entities. The efficiency of iKnow results in very rapid indexing—often several thousand notes (not an uncommon number) can be indexed in 20 to 30 seconds. iKnow responds to a user query by searching for specific terms or similar terms within the indexed text, and then displays these terms within the original source documents, similar to well-known commercial search engines. Structured data are indexed by the iFind program simultaneously with free-text indexing (Figure 1).

Security

Maintaining high levels of security of Health Insurance Portability and Accountability (HIPAA)-compliant information in an online application such as Voogle is critical to ensure trust of veterans and HCPs. All patient data accessed by Voogle reside within the secure firewall-protected VINCI environment. All moving information is protected with high-level encryption protocols (transport layer security [TLS]), and data at rest are also encrypted. As the application is online, no data are stored on the accessing device. Voogle uses a secure Microsoft Windows logon using VA Active Directory coupled with VistA authorization to regulate who can see the data and use the application. All access is audited, not only for “sensitive patients,” but also for specific data types. Users are reminded of this Voogle attribute on the home screen.

Accessing Voogle

Voogle is available on the VA intranet to all authorized users at https://voogle.vha.med.va.gov/voogle. To assure high-level security the application can only be accessed with the Internet Explorer browser using established user identification protocols to avoid unauthorized access or duplicative log-in tasks.

Indexing

Indexing is user-driven and is required prior to patient selection and term query. The user is prompted for a patient identifier and a date range. The CDW unique patient identifier is used for all internal processing. However, a social security number look-up table is incorporated to facilitate patient selection. The date field defaults to 3 years but can be extended to approximately the year 2000.

Queries

Entering the patient name in Lastname, Firstname (no space) format will yield a list of indexed patients. All access is audited in order to deter unauthorized queries. Data from a demonstration patient are displayed in Figures 2, 3, 4, 5,
and 6.

Structured Data Searches

Structured data categories that contain the queried term, as well as a term count, are displayed after the “Structured Data” toggle is selected (Figure 2). After the desired category (Figure 2: “Outpatient Rx”) is selected, Voogle accesses the data file and displays it as a grid (medication list, Figure 3). Filter and sort functions enable display of specific medications, drug classes, or date ranges (Figure 4).

Display of Terms Within Text Notes

Selecting a term from the drop-down list (Figure 5) opens a grid with the term highlighted in a snippet of text (Figure 6). Opening the document displays the context of the term, along with negation terms (ie, not, denies, no, etc) in red font if present. Voogle, unlike other NLP tools that attempt to interpret medical notes, relies on interpretation by the HCP user. Duplicate note fragments will be displayed in multiple notes, often across multiple screens, vividly demonstrating the pervasive use of the copy-and-paste text-entry strategy. Voogle satisfies 2 of the 4 recommendations of the recent report on copy-and-paste by Tsou and colleagues.⁹ The Voogle text display grid identifies copy-and-pasted text as well as establishes the provenance of the text (by sorting on the date column). Text can be copied from Voogle into an active Computerized Patient Record System (CPRS) note if needed for active patient care. Reindexing the following day and then repeating the search will demonstrate the newly copied-and-pasted text appended to the sequence.

Limitations

Voogle is unable to access all VA patient data currently. There are a dozen or so clinical domains that are indexed by Voogle that include prescriptions, problem lists, health factors, and others. More domains can be added with minimal effort and would then be available for fast search. The most critical deficiency is its inability to access, index, or query text reports stored as images within VistA Imaging. This includes nearly all reports from outside HCPs, emergency department visits or discharge summaries from unlinked hospitals, anesthesia reports, intensive care unit flow sheets, electrocardiograms, as well as numerous other text reports such as pulmonary function reports or sleep studies. Information that is transcribed by the provider into VistA as text (as in the case presented) is available within the CDW and can be found and displayed by Voogle search.

Voogle requires that the user initiates the indexing process prior to initiating the search process. Although Voogle defaults to 3 years prior to the current date, the user can specify a start date extending to close to the year 2000. The volume of data flowing into the CDW precludes automatic indexing of all patient data, as well as automatic updating of previously indexed data. We have explored the feasibility of queueing scheduled appointments for the following day, and although the strategy shows some promise, avoiding conflict with user-requested on-demand indexing remains challenging.

The current VA network architecture updates the CDW every night, resulting in up to a 24-hour delay in data availability. However, this delay should be reduced to several minutes after implementation of real-time data feeds accompanying the coming transition to a new EHR platform.

Conclusions

The recent introduction of the Joint Legacy Viewer (JLV) to the VA EHR desktop has enhanced the breadth of patient-specific information available to any VHA clinician, with recent enhancements providing access to some community care notes from outside HCPs. Voogle builds on this capability by enabling rapid search of text notes and structured data from multiple VA sites, over an extended time frame, and perhaps entered by hundreds of authors, as demonstrated in the case example. Formal usability and workload studies have not been performed; however, anecdotal reports indicate the application dramatically reduces the time required to search for critical information needed for care of complex patients who have been treated in multiple different VA hospitals and clinics.

The Voogle paradigm of leveraging patient information stored within a large enterprise-wide data warehouse through NLP techniques may be applicable to other systems as well, and warrants exploration. We believe that replacing traditional data search paradigms that require knowledge of data structure with a true query-based paradigm is a potential game changer for health information systems. Ultimately this strategy may help provide an antidote for the information chaos impacting HCP cognition. Moreover, reducing HCP cognitive load and time on task may lessen overall health care costs, reduce provider burn-out, and improve the quality of care received by patients.

Near real-time data feeds and adding additional clinical domains will potentially provide other benefits to patient care. For example, the authors plan to investigate whether sampling incoming data may assist with behind-the-scenes continuous monitoring of indicators of patient status to facilitate early warning of impending physiologic collapse.¹⁰ Other possible applications could include real-time scans for biosurveillance or other population screening requirements.

Acknowledgments
The authors express their sincere appreciation to Leslie DeYoung for documentation and Justin Wilson who constructed much of the graphical user interface for the Voogle application and design. Without their expertise, passion, and commitment the application would not be available as it is now.

Digitalization of patient-specific information over the past 2 decades has dramatically altered health care delivery. Nonetheless, this technology has yet to live up to its promise of improving patient outcomes, in part due to data storage challenges as well as the emphasis on data entry to support administrative and financial goals of the institution.^1-4 Substantially less emphasis has been placed on the retrieval of information required for accurate diagnosis.

A new search engine, Voogle, is now available through Microsoft Internet Explorer (Redmond, WA) to all providers in the US Department of Veterans Affairs (VA) on any intranet-enabled computer behind the VA firewall. Voogle facilitates rapid query-based search and retrieval of patient-specific data in the VA Corporate Data Warehouse (CDW).

Case Example

A veteran presented requesting consideration for implantation of a new device for obstructive sleep apnea. Guidelines for implantation of the new device specify a narrow therapeutic window, so determination of his apnea-hypopnea index (AHI) was critical. The patient had received care at more than 20 VA facilities and knew the approximate year the test had been performed at a non-VA facility.

A health care provider (HCP) using Voogle from his VA computer indexed all Veterans Information Systems and Technology Architecture (VistA) notes for the desired date range. The indexing of > 200 notes was completed in seconds. The HCP opened the indexed records with Voogle and entered a query for “sleep apnea,” which displayed multiple instances of the term within the patient record notes. A VA HCP had previously entered the data from the outside sleep study into a note shortly after the study.

This information was found immediately by sorting the indexed notes by date. The total time required by Voogle to find and display the critical information from the sleep study entered at a different VA more than a dozen years earlier was about 1 minute. These data provided the information needed for decision making at the time of the current patient encounter, without which repeat (and unnecessary) testing would have been required.

Information Overload

Electronic health records (EHRs) such as VistA, upload, store, collate, and present data in near real-time across multiple locations. Although the availability of these data can potentially reduce the risk of error due to missing critical information, its sheer volume limits its utility for point-of-care decision making. Much patient-specific text data found in clinical notes are recorded for administrative, financial, and business purposes rather than to support patient care decision making.^1-3 The majority of data documents processes of care rather than HCP observations, assessment of current status, or plans for care. Much of this text is inserted into templates, consists of imported structured data elements, and may contain repeated copy-and-paste free text.

Data uploaded to the CDW are aggregated from multiple hospitals, each with its own “instance” of VistA. Often the CDW contains thousands of text notes for a single patient. This volume of text may conceal critical historical information needed for patient care mixed with a plethora of duplicated or extraneous text entered to satisfy administrative requirements. The effects of information overload and poor system usability have been studied extensively in other disciplines, but this science has largely not been incorporated into EHR design.^1,3,4

A position paper published recently by the American College of Physicians notes that physician cognitive work is adversely impacted by the incorporation of nonclinical information into the EHR for use by other administrative and financial functions.²

Information Chaos

Beasley and colleagues noted that information in an EHR needed for optimal care may be unavailable, inadequate, scattered, conflicting, lost, or inaccurate, a condition they term information chaos.⁵ Smith and colleagues reported that decision making in 1 of 7 primary care visits was impaired by missing critical information. Surveyed HCPs estimated that 44% of patients with missing information may receive compromised care as a result, including delayed or erroneous diagnosis and increased costs due to duplication of diagnostic testing.⁶

Even when technically available, the usability of patient-specific data needed for accurate diagnosis is compromised if the HCP cannot find the information. In most systems data storage paradigms mirror database design rather than provider cognitive models. Ultimately, the design of current EHR interaction paradigms squanders precious cognitive resources and time, particularly during patient encounters, leaving little available for the cognitive tasks necessary for accurate diagnosis and treatment decisions.^1,3,4,7

VA Corporate Data Warehouse

VistA was implemented as a decentralized system with 130 instances, each of which is a freestanding EHR. However, as all systems share common data structures, the data can be combined from multiple instances when needed. The VA established a CDW more than 15 years ago in order to collate information from multiple sites to support operations as well as to seek new insights. The CDW currently updates nightly from all 130 EHR instances and is the only location in which patient information from all treating sites is combined. Voogle can access the CDW through the Veterans Informatics and Computing Infrastructure (VINCI), which is a mirror of the CDW databases and was established as a secure research environment.

The CDW contains information on 25 million veterans, with about 15 terabytes of text data. Approximately 4 billion data points, including 1 million text notes, are accrued nightly. The Integrated Control Number (ICN), a unique patient identifier, is assigned to each CDW record and is cross-indexed in the master patient index. All CDW data are tied to the ICN, facilitating access to and attribution of all patient data from all VA sites. Voogle relies on this identifier to build indexed files, or domains (which are document collections), of requested specific patient information to support its search algorithm.

Structured Data

Most of the data accrued in an EHR are structured data (such as laboratory test results and vital signs) and stored in a defined database framework. Voogle uses iFind (Intersystems Inc, Cambridge, MA) to index, count, and then search for requested information within structured data fields.

Unstructured Text

In contrast to structured data, text notes are stored as documents that are retrievable by patient, author, date, clinic, as well as numerous other fields. Unstructured (free) text notes are more information rich than either structured data or templated notes since their narrative format more closely parallels providers’ cognitive processes.^1,7 The value of the narrative becomes even more critical in understanding complex clinical scenarios with multiple interacting disease processes. Narratives emphasize important details, reducing cognitive overload by reducing the salience of detail the author deems to be less critical. Narrative notes simultaneously assure availability through the use of unstandardized language, often including specialty and disease-specific abbreviations.¹ Information needed for decision making in the illustrative case in this report was present only in HCP-entered free-text notes, as the structured data from which the free text was derived were not available.

Search

The introduction of search engines can be considered one of the major technologic disruptors of the 21st century.⁸ However, this advance has not yet made significant inroads into health care, despite advances in other domains. As of 2019, EHR users are still required to be familiar with the system’s data and menu structure in order to find needed information (or enter orders, code visits, or any of a number of tasks). Anecdotally, one of the authors (David Eibling) observed that the most common question from his trainees is “How do you . . .?” referring not to the care of the patient but rather to interaction with the EHR.

What is needed is a simple query-based application that finds the data on request. In addition to Voogle, other advances are being made in this arena such as the EMERSE, medical record search engine (project-emerse.org). Voogle was released to VA providers in 2017 and is available through the Internet Explorer browser on VA computers with VA intranet access. The goal of Voogle is to reduce HCP cognitive load by reducing the time and effort needed to seek relevant information for the care of a specific patient.

Natural Language Processing

Linguistic analysis of text seeking to understand its meaning constitutes a rapidly expanding field, with current heavy emphasis on the role of artificial intelligence and machine learning.¹ Advances in processing both structured data and free-text notes in the health care domain is in its infancy, despite the investment of considerable resources. Undoubtedly, advances in this arena will dramatically change provider cognitive work in the next decades.

VistA is coded in MUMPS (Massachusetts General Hospital Utility Multi-Programming System, also known as M), which has been in use for more than 50 years. Voogle employs iKnow, a novel natural language processing (NLP) application that resides in Caché (Intersystems, Boston, MA), the vendor-supported MUMPS infrastructure VistA uses to perform text analysis. iKnow does not attempt to interpret the meaning of text as do other common NLP applications, but instead relies on the expert user to interpret the meaning of the analyzed text. iKnow initially divides sentences into relations (usually verbs) and concepts, and then generates an index of these entities. The efficiency of iKnow results in very rapid indexing—often several thousand notes (not an uncommon number) can be indexed in 20 to 30 seconds. iKnow responds to a user query by searching for specific terms or similar terms within the indexed text, and then displays these terms within the original source documents, similar to well-known commercial search engines. Structured data are indexed by the iFind program simultaneously with free-text indexing (Figure 1).

Security

Maintaining high levels of security of Health Insurance Portability and Accountability (HIPAA)-compliant information in an online application such as Voogle is critical to ensure trust of veterans and HCPs. All patient data accessed by Voogle reside within the secure firewall-protected VINCI environment. All moving information is protected with high-level encryption protocols (transport layer security [TLS]), and data at rest are also encrypted. As the application is online, no data are stored on the accessing device. Voogle uses a secure Microsoft Windows logon using VA Active Directory coupled with VistA authorization to regulate who can see the data and use the application. All access is audited, not only for “sensitive patients,” but also for specific data types. Users are reminded of this Voogle attribute on the home screen.

Accessing Voogle

Voogle is available on the VA intranet to all authorized users at https://voogle.vha.med.va.gov/voogle. To assure high-level security the application can only be accessed with the Internet Explorer browser using established user identification protocols to avoid unauthorized access or duplicative log-in tasks.

Indexing

Indexing is user-driven and is required prior to patient selection and term query. The user is prompted for a patient identifier and a date range. The CDW unique patient identifier is used for all internal processing. However, a social security number look-up table is incorporated to facilitate patient selection. The date field defaults to 3 years but can be extended to approximately the year 2000.

Queries

Entering the patient name in Lastname, Firstname (no space) format will yield a list of indexed patients. All access is audited in order to deter unauthorized queries. Data from a demonstration patient are displayed in Figures 2, 3, 4, 5,
and 6.

Structured Data Searches

Structured data categories that contain the queried term, as well as a term count, are displayed after the “Structured Data” toggle is selected (Figure 2). After the desired category (Figure 2: “Outpatient Rx”) is selected, Voogle accesses the data file and displays it as a grid (medication list, Figure 3). Filter and sort functions enable display of specific medications, drug classes, or date ranges (Figure 4).

Display of Terms Within Text Notes

Selecting a term from the drop-down list (Figure 5) opens a grid with the term highlighted in a snippet of text (Figure 6). Opening the document displays the context of the term, along with negation terms (ie, not, denies, no, etc) in red font if present. Voogle, unlike other NLP tools that attempt to interpret medical notes, relies on interpretation by the HCP user. Duplicate note fragments will be displayed in multiple notes, often across multiple screens, vividly demonstrating the pervasive use of the copy-and-paste text-entry strategy. Voogle satisfies 2 of the 4 recommendations of the recent report on copy-and-paste by Tsou and colleagues.⁹ The Voogle text display grid identifies copy-and-pasted text as well as establishes the provenance of the text (by sorting on the date column). Text can be copied from Voogle into an active Computerized Patient Record System (CPRS) note if needed for active patient care. Reindexing the following day and then repeating the search will demonstrate the newly copied-and-pasted text appended to the sequence.

Limitations

Voogle is unable to access all VA patient data currently. There are a dozen or so clinical domains that are indexed by Voogle that include prescriptions, problem lists, health factors, and others. More domains can be added with minimal effort and would then be available for fast search. The most critical deficiency is its inability to access, index, or query text reports stored as images within VistA Imaging. This includes nearly all reports from outside HCPs, emergency department visits or discharge summaries from unlinked hospitals, anesthesia reports, intensive care unit flow sheets, electrocardiograms, as well as numerous other text reports such as pulmonary function reports or sleep studies. Information that is transcribed by the provider into VistA as text (as in the case presented) is available within the CDW and can be found and displayed by Voogle search.

Voogle requires that the user initiates the indexing process prior to initiating the search process. Although Voogle defaults to 3 years prior to the current date, the user can specify a start date extending to close to the year 2000. The volume of data flowing into the CDW precludes automatic indexing of all patient data, as well as automatic updating of previously indexed data. We have explored the feasibility of queueing scheduled appointments for the following day, and although the strategy shows some promise, avoiding conflict with user-requested on-demand indexing remains challenging.

The current VA network architecture updates the CDW every night, resulting in up to a 24-hour delay in data availability. However, this delay should be reduced to several minutes after implementation of real-time data feeds accompanying the coming transition to a new EHR platform.

Conclusions

The recent introduction of the Joint Legacy Viewer (JLV) to the VA EHR desktop has enhanced the breadth of patient-specific information available to any VHA clinician, with recent enhancements providing access to some community care notes from outside HCPs. Voogle builds on this capability by enabling rapid search of text notes and structured data from multiple VA sites, over an extended time frame, and perhaps entered by hundreds of authors, as demonstrated in the case example. Formal usability and workload studies have not been performed; however, anecdotal reports indicate the application dramatically reduces the time required to search for critical information needed for care of complex patients who have been treated in multiple different VA hospitals and clinics.

The Voogle paradigm of leveraging patient information stored within a large enterprise-wide data warehouse through NLP techniques may be applicable to other systems as well, and warrants exploration. We believe that replacing traditional data search paradigms that require knowledge of data structure with a true query-based paradigm is a potential game changer for health information systems. Ultimately this strategy may help provide an antidote for the information chaos impacting HCP cognition. Moreover, reducing HCP cognitive load and time on task may lessen overall health care costs, reduce provider burn-out, and improve the quality of care received by patients.

Near real-time data feeds and adding additional clinical domains will potentially provide other benefits to patient care. For example, the authors plan to investigate whether sampling incoming data may assist with behind-the-scenes continuous monitoring of indicators of patient status to facilitate early warning of impending physiologic collapse.¹⁰ Other possible applications could include real-time scans for biosurveillance or other population screening requirements.

Acknowledgments
The authors express their sincere appreciation to Leslie DeYoung for documentation and Justin Wilson who constructed much of the graphical user interface for the Voogle application and design. Without their expertise, passion, and commitment the application would not be available as it is now.

Digitalization of patient-specific information over the past 2 decades has dramatically altered health care delivery. Nonetheless, this technology has yet to live up to its promise of improving patient outcomes, in part due to data storage challenges as well as the emphasis on data entry to support administrative and financial goals of the institution.^1-4 Substantially less emphasis has been placed on the retrieval of information required for accurate diagnosis.

A new search engine, Voogle, is now available through Microsoft Internet Explorer (Redmond, WA) to all providers in the US Department of Veterans Affairs (VA) on any intranet-enabled computer behind the VA firewall. Voogle facilitates rapid query-based search and retrieval of patient-specific data in the VA Corporate Data Warehouse (CDW).

Case Example

A veteran presented requesting consideration for implantation of a new device for obstructive sleep apnea. Guidelines for implantation of the new device specify a narrow therapeutic window, so determination of his apnea-hypopnea index (AHI) was critical. The patient had received care at more than 20 VA facilities and knew the approximate year the test had been performed at a non-VA facility.

A health care provider (HCP) using Voogle from his VA computer indexed all Veterans Information Systems and Technology Architecture (VistA) notes for the desired date range. The indexing of > 200 notes was completed in seconds. The HCP opened the indexed records with Voogle and entered a query for “sleep apnea,” which displayed multiple instances of the term within the patient record notes. A VA HCP had previously entered the data from the outside sleep study into a note shortly after the study.

This information was found immediately by sorting the indexed notes by date. The total time required by Voogle to find and display the critical information from the sleep study entered at a different VA more than a dozen years earlier was about 1 minute. These data provided the information needed for decision making at the time of the current patient encounter, without which repeat (and unnecessary) testing would have been required.

Information Overload

Electronic health records (EHRs) such as VistA, upload, store, collate, and present data in near real-time across multiple locations. Although the availability of these data can potentially reduce the risk of error due to missing critical information, its sheer volume limits its utility for point-of-care decision making. Much patient-specific text data found in clinical notes are recorded for administrative, financial, and business purposes rather than to support patient care decision making.^1-3 The majority of data documents processes of care rather than HCP observations, assessment of current status, or plans for care. Much of this text is inserted into templates, consists of imported structured data elements, and may contain repeated copy-and-paste free text.

Data uploaded to the CDW are aggregated from multiple hospitals, each with its own “instance” of VistA. Often the CDW contains thousands of text notes for a single patient. This volume of text may conceal critical historical information needed for patient care mixed with a plethora of duplicated or extraneous text entered to satisfy administrative requirements. The effects of information overload and poor system usability have been studied extensively in other disciplines, but this science has largely not been incorporated into EHR design.^1,3,4

A position paper published recently by the American College of Physicians notes that physician cognitive work is adversely impacted by the incorporation of nonclinical information into the EHR for use by other administrative and financial functions.²

Information Chaos

Beasley and colleagues noted that information in an EHR needed for optimal care may be unavailable, inadequate, scattered, conflicting, lost, or inaccurate, a condition they term information chaos.⁵ Smith and colleagues reported that decision making in 1 of 7 primary care visits was impaired by missing critical information. Surveyed HCPs estimated that 44% of patients with missing information may receive compromised care as a result, including delayed or erroneous diagnosis and increased costs due to duplication of diagnostic testing.⁶

Even when technically available, the usability of patient-specific data needed for accurate diagnosis is compromised if the HCP cannot find the information. In most systems data storage paradigms mirror database design rather than provider cognitive models. Ultimately, the design of current EHR interaction paradigms squanders precious cognitive resources and time, particularly during patient encounters, leaving little available for the cognitive tasks necessary for accurate diagnosis and treatment decisions.^1,3,4,7

VA Corporate Data Warehouse

VistA was implemented as a decentralized system with 130 instances, each of which is a freestanding EHR. However, as all systems share common data structures, the data can be combined from multiple instances when needed. The VA established a CDW more than 15 years ago in order to collate information from multiple sites to support operations as well as to seek new insights. The CDW currently updates nightly from all 130 EHR instances and is the only location in which patient information from all treating sites is combined. Voogle can access the CDW through the Veterans Informatics and Computing Infrastructure (VINCI), which is a mirror of the CDW databases and was established as a secure research environment.

The CDW contains information on 25 million veterans, with about 15 terabytes of text data. Approximately 4 billion data points, including 1 million text notes, are accrued nightly. The Integrated Control Number (ICN), a unique patient identifier, is assigned to each CDW record and is cross-indexed in the master patient index. All CDW data are tied to the ICN, facilitating access to and attribution of all patient data from all VA sites. Voogle relies on this identifier to build indexed files, or domains (which are document collections), of requested specific patient information to support its search algorithm.

Structured Data

Most of the data accrued in an EHR are structured data (such as laboratory test results and vital signs) and stored in a defined database framework. Voogle uses iFind (Intersystems Inc, Cambridge, MA) to index, count, and then search for requested information within structured data fields.

Unstructured Text

In contrast to structured data, text notes are stored as documents that are retrievable by patient, author, date, clinic, as well as numerous other fields. Unstructured (free) text notes are more information rich than either structured data or templated notes since their narrative format more closely parallels providers’ cognitive processes.^1,7 The value of the narrative becomes even more critical in understanding complex clinical scenarios with multiple interacting disease processes. Narratives emphasize important details, reducing cognitive overload by reducing the salience of detail the author deems to be less critical. Narrative notes simultaneously assure availability through the use of unstandardized language, often including specialty and disease-specific abbreviations.¹ Information needed for decision making in the illustrative case in this report was present only in HCP-entered free-text notes, as the structured data from which the free text was derived were not available.

Search

The introduction of search engines can be considered one of the major technologic disruptors of the 21st century.⁸ However, this advance has not yet made significant inroads into health care, despite advances in other domains. As of 2019, EHR users are still required to be familiar with the system’s data and menu structure in order to find needed information (or enter orders, code visits, or any of a number of tasks). Anecdotally, one of the authors (David Eibling) observed that the most common question from his trainees is “How do you . . .?” referring not to the care of the patient but rather to interaction with the EHR.

What is needed is a simple query-based application that finds the data on request. In addition to Voogle, other advances are being made in this arena such as the EMERSE, medical record search engine (project-emerse.org). Voogle was released to VA providers in 2017 and is available through the Internet Explorer browser on VA computers with VA intranet access. The goal of Voogle is to reduce HCP cognitive load by reducing the time and effort needed to seek relevant information for the care of a specific patient.

Natural Language Processing

Linguistic analysis of text seeking to understand its meaning constitutes a rapidly expanding field, with current heavy emphasis on the role of artificial intelligence and machine learning.¹ Advances in processing both structured data and free-text notes in the health care domain is in its infancy, despite the investment of considerable resources. Undoubtedly, advances in this arena will dramatically change provider cognitive work in the next decades.

VistA is coded in MUMPS (Massachusetts General Hospital Utility Multi-Programming System, also known as M), which has been in use for more than 50 years. Voogle employs iKnow, a novel natural language processing (NLP) application that resides in Caché (Intersystems, Boston, MA), the vendor-supported MUMPS infrastructure VistA uses to perform text analysis. iKnow does not attempt to interpret the meaning of text as do other common NLP applications, but instead relies on the expert user to interpret the meaning of the analyzed text. iKnow initially divides sentences into relations (usually verbs) and concepts, and then generates an index of these entities. The efficiency of iKnow results in very rapid indexing—often several thousand notes (not an uncommon number) can be indexed in 20 to 30 seconds. iKnow responds to a user query by searching for specific terms or similar terms within the indexed text, and then displays these terms within the original source documents, similar to well-known commercial search engines. Structured data are indexed by the iFind program simultaneously with free-text indexing (Figure 1).

Security

Maintaining high levels of security of Health Insurance Portability and Accountability (HIPAA)-compliant information in an online application such as Voogle is critical to ensure trust of veterans and HCPs. All patient data accessed by Voogle reside within the secure firewall-protected VINCI environment. All moving information is protected with high-level encryption protocols (transport layer security [TLS]), and data at rest are also encrypted. As the application is online, no data are stored on the accessing device. Voogle uses a secure Microsoft Windows logon using VA Active Directory coupled with VistA authorization to regulate who can see the data and use the application. All access is audited, not only for “sensitive patients,” but also for specific data types. Users are reminded of this Voogle attribute on the home screen.

Accessing Voogle

Voogle is available on the VA intranet to all authorized users at https://voogle.vha.med.va.gov/voogle. To assure high-level security the application can only be accessed with the Internet Explorer browser using established user identification protocols to avoid unauthorized access or duplicative log-in tasks.

Indexing

Indexing is user-driven and is required prior to patient selection and term query. The user is prompted for a patient identifier and a date range. The CDW unique patient identifier is used for all internal processing. However, a social security number look-up table is incorporated to facilitate patient selection. The date field defaults to 3 years but can be extended to approximately the year 2000.

Queries

Entering the patient name in Lastname, Firstname (no space) format will yield a list of indexed patients. All access is audited in order to deter unauthorized queries. Data from a demonstration patient are displayed in Figures 2, 3, 4, 5,
and 6.

Structured Data Searches

Structured data categories that contain the queried term, as well as a term count, are displayed after the “Structured Data” toggle is selected (Figure 2). After the desired category (Figure 2: “Outpatient Rx”) is selected, Voogle accesses the data file and displays it as a grid (medication list, Figure 3). Filter and sort functions enable display of specific medications, drug classes, or date ranges (Figure 4).

Display of Terms Within Text Notes

Selecting a term from the drop-down list (Figure 5) opens a grid with the term highlighted in a snippet of text (Figure 6). Opening the document displays the context of the term, along with negation terms (ie, not, denies, no, etc) in red font if present. Voogle, unlike other NLP tools that attempt to interpret medical notes, relies on interpretation by the HCP user. Duplicate note fragments will be displayed in multiple notes, often across multiple screens, vividly demonstrating the pervasive use of the copy-and-paste text-entry strategy. Voogle satisfies 2 of the 4 recommendations of the recent report on copy-and-paste by Tsou and colleagues.⁹ The Voogle text display grid identifies copy-and-pasted text as well as establishes the provenance of the text (by sorting on the date column). Text can be copied from Voogle into an active Computerized Patient Record System (CPRS) note if needed for active patient care. Reindexing the following day and then repeating the search will demonstrate the newly copied-and-pasted text appended to the sequence.

Limitations

Voogle is unable to access all VA patient data currently. There are a dozen or so clinical domains that are indexed by Voogle that include prescriptions, problem lists, health factors, and others. More domains can be added with minimal effort and would then be available for fast search. The most critical deficiency is its inability to access, index, or query text reports stored as images within VistA Imaging. This includes nearly all reports from outside HCPs, emergency department visits or discharge summaries from unlinked hospitals, anesthesia reports, intensive care unit flow sheets, electrocardiograms, as well as numerous other text reports such as pulmonary function reports or sleep studies. Information that is transcribed by the provider into VistA as text (as in the case presented) is available within the CDW and can be found and displayed by Voogle search.

Voogle requires that the user initiates the indexing process prior to initiating the search process. Although Voogle defaults to 3 years prior to the current date, the user can specify a start date extending to close to the year 2000. The volume of data flowing into the CDW precludes automatic indexing of all patient data, as well as automatic updating of previously indexed data. We have explored the feasibility of queueing scheduled appointments for the following day, and although the strategy shows some promise, avoiding conflict with user-requested on-demand indexing remains challenging.

The current VA network architecture updates the CDW every night, resulting in up to a 24-hour delay in data availability. However, this delay should be reduced to several minutes after implementation of real-time data feeds accompanying the coming transition to a new EHR platform.

Conclusions

The recent introduction of the Joint Legacy Viewer (JLV) to the VA EHR desktop has enhanced the breadth of patient-specific information available to any VHA clinician, with recent enhancements providing access to some community care notes from outside HCPs. Voogle builds on this capability by enabling rapid search of text notes and structured data from multiple VA sites, over an extended time frame, and perhaps entered by hundreds of authors, as demonstrated in the case example. Formal usability and workload studies have not been performed; however, anecdotal reports indicate the application dramatically reduces the time required to search for critical information needed for care of complex patients who have been treated in multiple different VA hospitals and clinics.

The Voogle paradigm of leveraging patient information stored within a large enterprise-wide data warehouse through NLP techniques may be applicable to other systems as well, and warrants exploration. We believe that replacing traditional data search paradigms that require knowledge of data structure with a true query-based paradigm is a potential game changer for health information systems. Ultimately this strategy may help provide an antidote for the information chaos impacting HCP cognition. Moreover, reducing HCP cognitive load and time on task may lessen overall health care costs, reduce provider burn-out, and improve the quality of care received by patients.

Near real-time data feeds and adding additional clinical domains will potentially provide other benefits to patient care. For example, the authors plan to investigate whether sampling incoming data may assist with behind-the-scenes continuous monitoring of indicators of patient status to facilitate early warning of impending physiologic collapse.¹⁰ Other possible applications could include real-time scans for biosurveillance or other population screening requirements.

Acknowledgments
The authors express their sincere appreciation to Leslie DeYoung for documentation and Justin Wilson who constructed much of the graphical user interface for the Voogle application and design. Without their expertise, passion, and commitment the application would not be available as it is now.

On the 11th day of the 11th month, we celebrate Veterans Day (no apostrophe because it is not a day that veterans possess or that belongs to any individual veteran).^2,3 Interestingly, the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA) have web pages correcting any confusion about the meaning of Memorial Day and Veterans Day so that the public understands the unique purpose of each holiday. Memorial Day commemorates all those who lost their lives in the line of duty to the nation, whereas Veterans Day commemorates all those who have honorably served their country as service members. While Memorial Day is a solemn occasion of remembering and respect for those who have died, Veterans Day is an event of gratitude and appreciation focused on veterans still living. The dual mission of the 2 holidays is to remind the public of the debt of remembrance and reverence we owe all veterans both those who have gone before us and those who remain with us.

Memory is what most intrinsically unites the 2 commemorations. In fact, in Great Britain, Canada, and Australia, November 11 is called Remembrance Day.² Yet memory is a double-edged sword that can be raised in tribute to service members or can deeply lacerate them. Many of the wounds that cause the most prolonged and deepest suffering are not physical—they are mental. Disturbances of memory are among the criteria for posttraumatic stress disorder (PTSD). Under its section on intrusive cluster, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) lists “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).” The avoidance cluster underscores how the afflicted mind tries to escape itself: “Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).”⁴

PTSD was first recognized as a psychiatric diagnosis in DSM-III in 1980, and since then VA and DoD have devoted enormous resources to developing effective treatments for the disorder, most notably evidence-based psychotherapies. Sadly ironic, the only psychiatric disorder whose etiology is understood has proved to be the most difficult to treat much less cure. As with most serious mental illnesses, some cases become chronic and refractory to the best of care. These tormented individuals live as if in a twilight zone between the past and the present.

Memory and war have a long history in literature, poetry, and history. Haunting memories of PTSD are found in the ancient epics of Homer. On the long treacherous journey home from sacking Troy, Odysseus and his army arrive in the land of the Lotus-eaters, where native sweet fruit induces a state of timeless forgetfulness in which torment and tragedy dissolve along with motivation and meaning.⁵ Jonathan Shay, VA psychiatrist and pioneer of the Homer-PTSD connection, suggested the analogy between the land of the Lotus-eaters and addiction: Each is a self-medication of the psychic aftermath of war.⁶

But what if those devastating memories could be selectively erased or even better blocked before they were formed? Although this solution may seem like science fiction, research into these possibilities is in reality science fact. Over the past decades, the DoD and the VA have sought such a neuroscience jewel in the lotus. Studies in rodents and humans have looked at the ability of a number of medications, most recently β blockers, such as propranolol, to interfere with the consolidation of emotionally traumatic memories (memory erasure) and disrupting their retention once consolidated (memory extinction).⁷ While researchers cannot yet completely wipe out a selected memory, like in the movie Star Trek, it has been shown that medications at least in study settings do reduce fear and can attenuate the development of PTSD when combined with psychotherapy. Neuroscientists call these more realistic alterations of recall memory dampening. Though these medications are not ready for regular clinical application, the unprecedented pace of neuroscience makes it nearly inevitable that in the not so distant future some significant blunting of traumatic memory will be possible.

Once science answers in the affirmative the question, “Is this intervention something we could conceivably do?” The next question belongs to ethics, “Is this intervention something we should do even if we can?” As early as 2001, the President’s Council on Bioethics answered the latter with “probably not.”

Use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory....Thus, by blunting the emotional impact of events, beta-blockers or their successors would concomitantly weaken our recollection of the traumatic events we have just experienced. Yet often it is important in the after of such events that at least someone remember them clearly. For legal reasons, to say nothing of deeper social and personal ones, the wisdom of routinely interfering with the memories of traumatic survivors and witnesses is highly questionable.⁸

Many neuroscientists and neuroethicists objected to the perspective of the Bioethics Council as being too puritanical and its position overly pessimistic:

Whereas memory dampening has its drawbacks, such may be the price we pay in order to heal immense suffering. In some contexts, there may be steps that ought to be taken to preserve valuable factual or emotional information contained in memory, even when we must delay or otherwise impose limits on access to memory dampening. None of these concerns, however, even if they find empirical support, are strong enough to justify brushed restrictions on memory dampening.⁹

The proponents of the 2 views propose and oppose the contrarian position on issues both philosophical and practical, such as the function of traumatic experience in personal growth; how the preservation of memory is related to the integrity of the person and authenticity of the life lived; how blunting of memories of especially combat trauma may normalize our reactions to suffering and evil; and most important for this Veterans Day essay, whether remembering is an ethical duty and if so whose is it to discharge, the individual, his family, community, or country.

More pragmatic, there would be a need to refine our understanding of the risk factors for chronic and disabling PTSD; to determine when in the course of the trauma experience to pharmacologically interfere with memory and to what degree and scope; how to protect the autonomy of the service member to consent or to refuse the procedure within the recognized confines of military ethics; and most important for this essay, how to prevent governments, corporations, or any other entity from exploiting neurobiologic discoveries for power or profit.

Elie Wiesel is an important modern prophet of the critical role of memory in the survival of civilization. His prophecy is rooted in the incomprehensible anguish and horror he personally and communally witnessed in the Holocaust. He suggests in this editorial’s epigraph that there are deep and profound issues to be pondered about memory and its inextricable link to suffering. Meditations offer thoughts, not answers, and I encourage readers to spend a few minutes considering the solemn ones presented here this Veterans Day.

On the 11th day of the 11th month, we celebrate Veterans Day (no apostrophe because it is not a day that veterans possess or that belongs to any individual veteran).^2,3 Interestingly, the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA) have web pages correcting any confusion about the meaning of Memorial Day and Veterans Day so that the public understands the unique purpose of each holiday. Memorial Day commemorates all those who lost their lives in the line of duty to the nation, whereas Veterans Day commemorates all those who have honorably served their country as service members. While Memorial Day is a solemn occasion of remembering and respect for those who have died, Veterans Day is an event of gratitude and appreciation focused on veterans still living. The dual mission of the 2 holidays is to remind the public of the debt of remembrance and reverence we owe all veterans both those who have gone before us and those who remain with us.

Memory is what most intrinsically unites the 2 commemorations. In fact, in Great Britain, Canada, and Australia, November 11 is called Remembrance Day.² Yet memory is a double-edged sword that can be raised in tribute to service members or can deeply lacerate them. Many of the wounds that cause the most prolonged and deepest suffering are not physical—they are mental. Disturbances of memory are among the criteria for posttraumatic stress disorder (PTSD). Under its section on intrusive cluster, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) lists “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).” The avoidance cluster underscores how the afflicted mind tries to escape itself: “Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).”⁴

PTSD was first recognized as a psychiatric diagnosis in DSM-III in 1980, and since then VA and DoD have devoted enormous resources to developing effective treatments for the disorder, most notably evidence-based psychotherapies. Sadly ironic, the only psychiatric disorder whose etiology is understood has proved to be the most difficult to treat much less cure. As with most serious mental illnesses, some cases become chronic and refractory to the best of care. These tormented individuals live as if in a twilight zone between the past and the present.

Memory and war have a long history in literature, poetry, and history. Haunting memories of PTSD are found in the ancient epics of Homer. On the long treacherous journey home from sacking Troy, Odysseus and his army arrive in the land of the Lotus-eaters, where native sweet fruit induces a state of timeless forgetfulness in which torment and tragedy dissolve along with motivation and meaning.⁵ Jonathan Shay, VA psychiatrist and pioneer of the Homer-PTSD connection, suggested the analogy between the land of the Lotus-eaters and addiction: Each is a self-medication of the psychic aftermath of war.⁶

But what if those devastating memories could be selectively erased or even better blocked before they were formed? Although this solution may seem like science fiction, research into these possibilities is in reality science fact. Over the past decades, the DoD and the VA have sought such a neuroscience jewel in the lotus. Studies in rodents and humans have looked at the ability of a number of medications, most recently β blockers, such as propranolol, to interfere with the consolidation of emotionally traumatic memories (memory erasure) and disrupting their retention once consolidated (memory extinction).⁷ While researchers cannot yet completely wipe out a selected memory, like in the movie Star Trek, it has been shown that medications at least in study settings do reduce fear and can attenuate the development of PTSD when combined with psychotherapy. Neuroscientists call these more realistic alterations of recall memory dampening. Though these medications are not ready for regular clinical application, the unprecedented pace of neuroscience makes it nearly inevitable that in the not so distant future some significant blunting of traumatic memory will be possible.

Once science answers in the affirmative the question, “Is this intervention something we could conceivably do?” The next question belongs to ethics, “Is this intervention something we should do even if we can?” As early as 2001, the President’s Council on Bioethics answered the latter with “probably not.”

Use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory....Thus, by blunting the emotional impact of events, beta-blockers or their successors would concomitantly weaken our recollection of the traumatic events we have just experienced. Yet often it is important in the after of such events that at least someone remember them clearly. For legal reasons, to say nothing of deeper social and personal ones, the wisdom of routinely interfering with the memories of traumatic survivors and witnesses is highly questionable.⁸

Many neuroscientists and neuroethicists objected to the perspective of the Bioethics Council as being too puritanical and its position overly pessimistic:

Whereas memory dampening has its drawbacks, such may be the price we pay in order to heal immense suffering. In some contexts, there may be steps that ought to be taken to preserve valuable factual or emotional information contained in memory, even when we must delay or otherwise impose limits on access to memory dampening. None of these concerns, however, even if they find empirical support, are strong enough to justify brushed restrictions on memory dampening.⁹

The proponents of the 2 views propose and oppose the contrarian position on issues both philosophical and practical, such as the function of traumatic experience in personal growth; how the preservation of memory is related to the integrity of the person and authenticity of the life lived; how blunting of memories of especially combat trauma may normalize our reactions to suffering and evil; and most important for this Veterans Day essay, whether remembering is an ethical duty and if so whose is it to discharge, the individual, his family, community, or country.

More pragmatic, there would be a need to refine our understanding of the risk factors for chronic and disabling PTSD; to determine when in the course of the trauma experience to pharmacologically interfere with memory and to what degree and scope; how to protect the autonomy of the service member to consent or to refuse the procedure within the recognized confines of military ethics; and most important for this essay, how to prevent governments, corporations, or any other entity from exploiting neurobiologic discoveries for power or profit.

Elie Wiesel is an important modern prophet of the critical role of memory in the survival of civilization. His prophecy is rooted in the incomprehensible anguish and horror he personally and communally witnessed in the Holocaust. He suggests in this editorial’s epigraph that there are deep and profound issues to be pondered about memory and its inextricable link to suffering. Meditations offer thoughts, not answers, and I encourage readers to spend a few minutes considering the solemn ones presented here this Veterans Day.

On the 11th day of the 11th month, we celebrate Veterans Day (no apostrophe because it is not a day that veterans possess or that belongs to any individual veteran).^2,3 Interestingly, the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA) have web pages correcting any confusion about the meaning of Memorial Day and Veterans Day so that the public understands the unique purpose of each holiday. Memorial Day commemorates all those who lost their lives in the line of duty to the nation, whereas Veterans Day commemorates all those who have honorably served their country as service members. While Memorial Day is a solemn occasion of remembering and respect for those who have died, Veterans Day is an event of gratitude and appreciation focused on veterans still living. The dual mission of the 2 holidays is to remind the public of the debt of remembrance and reverence we owe all veterans both those who have gone before us and those who remain with us.

Memory is what most intrinsically unites the 2 commemorations. In fact, in Great Britain, Canada, and Australia, November 11 is called Remembrance Day.² Yet memory is a double-edged sword that can be raised in tribute to service members or can deeply lacerate them. Many of the wounds that cause the most prolonged and deepest suffering are not physical—they are mental. Disturbances of memory are among the criteria for posttraumatic stress disorder (PTSD). Under its section on intrusive cluster, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) lists “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).” The avoidance cluster underscores how the afflicted mind tries to escape itself: “Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).”⁴

PTSD was first recognized as a psychiatric diagnosis in DSM-III in 1980, and since then VA and DoD have devoted enormous resources to developing effective treatments for the disorder, most notably evidence-based psychotherapies. Sadly ironic, the only psychiatric disorder whose etiology is understood has proved to be the most difficult to treat much less cure. As with most serious mental illnesses, some cases become chronic and refractory to the best of care. These tormented individuals live as if in a twilight zone between the past and the present.

Memory and war have a long history in literature, poetry, and history. Haunting memories of PTSD are found in the ancient epics of Homer. On the long treacherous journey home from sacking Troy, Odysseus and his army arrive in the land of the Lotus-eaters, where native sweet fruit induces a state of timeless forgetfulness in which torment and tragedy dissolve along with motivation and meaning.⁵ Jonathan Shay, VA psychiatrist and pioneer of the Homer-PTSD connection, suggested the analogy between the land of the Lotus-eaters and addiction: Each is a self-medication of the psychic aftermath of war.⁶

But what if those devastating memories could be selectively erased or even better blocked before they were formed? Although this solution may seem like science fiction, research into these possibilities is in reality science fact. Over the past decades, the DoD and the VA have sought such a neuroscience jewel in the lotus. Studies in rodents and humans have looked at the ability of a number of medications, most recently β blockers, such as propranolol, to interfere with the consolidation of emotionally traumatic memories (memory erasure) and disrupting their retention once consolidated (memory extinction).⁷ While researchers cannot yet completely wipe out a selected memory, like in the movie Star Trek, it has been shown that medications at least in study settings do reduce fear and can attenuate the development of PTSD when combined with psychotherapy. Neuroscientists call these more realistic alterations of recall memory dampening. Though these medications are not ready for regular clinical application, the unprecedented pace of neuroscience makes it nearly inevitable that in the not so distant future some significant blunting of traumatic memory will be possible.

Once science answers in the affirmative the question, “Is this intervention something we could conceivably do?” The next question belongs to ethics, “Is this intervention something we should do even if we can?” As early as 2001, the President’s Council on Bioethics answered the latter with “probably not.”

Use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory....Thus, by blunting the emotional impact of events, beta-blockers or their successors would concomitantly weaken our recollection of the traumatic events we have just experienced. Yet often it is important in the after of such events that at least someone remember them clearly. For legal reasons, to say nothing of deeper social and personal ones, the wisdom of routinely interfering with the memories of traumatic survivors and witnesses is highly questionable.⁸

Many neuroscientists and neuroethicists objected to the perspective of the Bioethics Council as being too puritanical and its position overly pessimistic:

Whereas memory dampening has its drawbacks, such may be the price we pay in order to heal immense suffering. In some contexts, there may be steps that ought to be taken to preserve valuable factual or emotional information contained in memory, even when we must delay or otherwise impose limits on access to memory dampening. None of these concerns, however, even if they find empirical support, are strong enough to justify brushed restrictions on memory dampening.⁹

The proponents of the 2 views propose and oppose the contrarian position on issues both philosophical and practical, such as the function of traumatic experience in personal growth; how the preservation of memory is related to the integrity of the person and authenticity of the life lived; how blunting of memories of especially combat trauma may normalize our reactions to suffering and evil; and most important for this Veterans Day essay, whether remembering is an ethical duty and if so whose is it to discharge, the individual, his family, community, or country.

More pragmatic, there would be a need to refine our understanding of the risk factors for chronic and disabling PTSD; to determine when in the course of the trauma experience to pharmacologically interfere with memory and to what degree and scope; how to protect the autonomy of the service member to consent or to refuse the procedure within the recognized confines of military ethics; and most important for this essay, how to prevent governments, corporations, or any other entity from exploiting neurobiologic discoveries for power or profit.

Elie Wiesel is an important modern prophet of the critical role of memory in the survival of civilization. His prophecy is rooted in the incomprehensible anguish and horror he personally and communally witnessed in the Holocaust. He suggests in this editorial’s epigraph that there are deep and profound issues to be pondered about memory and its inextricable link to suffering. Meditations offer thoughts, not answers, and I encourage readers to spend a few minutes considering the solemn ones presented here this Veterans Day.

When we studied the knowledge and practice of e-cigarette use among pregnant women in one of our outpatient practices, we found that 43% of more than 300 survey participants believed e-cigarettes are less harmful to a fetus than traditional cigarettes. Just over half – 57% – believed that e-cigarettes contain nicotine.

This study from 5 years ago demonstrated the need for more patient education.¹ Today, we have even more clarity that, while there may be health benefits of switching to noncombustible forms of nicotine consumption outside of pregnancy, these potential benefits do not extend to pregnancy. Both human and animal studies have demonstrated that nicotine itself is harmful to the developing fetus; the Centers for Disease Control and Prevention warns against the use of e-cigarettes in pregnancy for this reason.

A 2018 literature review on the use of e-cigarettes in pregnancy and the effects on perinatal/neonatal outcomes reported that the amount of nicotine consumed by e-cigarette users is similar to that of cigarette smokers and that most animal studies suggest a potential danger to the fetus, primarily because of the nicotine.² Effects on the immune system, neural development, lung function, and cardiac function were all noted in the review. Other research has shown that e-cigarette fluid can contain formaldehyde and other harmful substances.

A new analysis of data from the 2014-2017 National Health Interview Survey shows a significantly lower prevalence of conventional cigarette use among pregnant women than in nonpregnant women, and an almost identical prevalence of e-cigarette use among pregnant and nonpregnant women of reproductive age.³ This discrepancy again suggests that women may not be aware of the potential harms of e-cigarettes in pregnancy, which is not surprising considering that prenatal care clinicians often are not appropriately screening or counseling regarding e-cigarette use.⁴

We must specifically ask about vaping and e-cigarette use as part of our prenatal care and counsel women that the use of e-cigarettes is not a safer alternative to cigarette smoking. I urge patients who have switched to e-cigarettes as a means of smoking cessation or as a choice they perceive to be safer to work together with me to find another way to reduce potential harm to their baby.

References

1. J Addict Med. 2015 Jul-Aug;9(4):266-72.

2. Obstet Gynecol Surv. 2018 Sep;73(9):544-9.

3. JAMA Pediatr. 2019 Jun 1;173(6):600-2.

4. Am J Obstet Gynecol. 2014 Dec;211(6):695.e1-7.

When we studied the knowledge and practice of e-cigarette use among pregnant women in one of our outpatient practices, we found that 43% of more than 300 survey participants believed e-cigarettes are less harmful to a fetus than traditional cigarettes. Just over half – 57% – believed that e-cigarettes contain nicotine.

This study from 5 years ago demonstrated the need for more patient education.¹ Today, we have even more clarity that, while there may be health benefits of switching to noncombustible forms of nicotine consumption outside of pregnancy, these potential benefits do not extend to pregnancy. Both human and animal studies have demonstrated that nicotine itself is harmful to the developing fetus; the Centers for Disease Control and Prevention warns against the use of e-cigarettes in pregnancy for this reason.

A 2018 literature review on the use of e-cigarettes in pregnancy and the effects on perinatal/neonatal outcomes reported that the amount of nicotine consumed by e-cigarette users is similar to that of cigarette smokers and that most animal studies suggest a potential danger to the fetus, primarily because of the nicotine.² Effects on the immune system, neural development, lung function, and cardiac function were all noted in the review. Other research has shown that e-cigarette fluid can contain formaldehyde and other harmful substances.

A new analysis of data from the 2014-2017 National Health Interview Survey shows a significantly lower prevalence of conventional cigarette use among pregnant women than in nonpregnant women, and an almost identical prevalence of e-cigarette use among pregnant and nonpregnant women of reproductive age.³ This discrepancy again suggests that women may not be aware of the potential harms of e-cigarettes in pregnancy, which is not surprising considering that prenatal care clinicians often are not appropriately screening or counseling regarding e-cigarette use.⁴

We must specifically ask about vaping and e-cigarette use as part of our prenatal care and counsel women that the use of e-cigarettes is not a safer alternative to cigarette smoking. I urge patients who have switched to e-cigarettes as a means of smoking cessation or as a choice they perceive to be safer to work together with me to find another way to reduce potential harm to their baby.

References

1. J Addict Med. 2015 Jul-Aug;9(4):266-72.

2. Obstet Gynecol Surv. 2018 Sep;73(9):544-9.

3. JAMA Pediatr. 2019 Jun 1;173(6):600-2.

4. Am J Obstet Gynecol. 2014 Dec;211(6):695.e1-7.

When we studied the knowledge and practice of e-cigarette use among pregnant women in one of our outpatient practices, we found that 43% of more than 300 survey participants believed e-cigarettes are less harmful to a fetus than traditional cigarettes. Just over half – 57% – believed that e-cigarettes contain nicotine.

This study from 5 years ago demonstrated the need for more patient education.¹ Today, we have even more clarity that, while there may be health benefits of switching to noncombustible forms of nicotine consumption outside of pregnancy, these potential benefits do not extend to pregnancy. Both human and animal studies have demonstrated that nicotine itself is harmful to the developing fetus; the Centers for Disease Control and Prevention warns against the use of e-cigarettes in pregnancy for this reason.

A 2018 literature review on the use of e-cigarettes in pregnancy and the effects on perinatal/neonatal outcomes reported that the amount of nicotine consumed by e-cigarette users is similar to that of cigarette smokers and that most animal studies suggest a potential danger to the fetus, primarily because of the nicotine.² Effects on the immune system, neural development, lung function, and cardiac function were all noted in the review. Other research has shown that e-cigarette fluid can contain formaldehyde and other harmful substances.

A new analysis of data from the 2014-2017 National Health Interview Survey shows a significantly lower prevalence of conventional cigarette use among pregnant women than in nonpregnant women, and an almost identical prevalence of e-cigarette use among pregnant and nonpregnant women of reproductive age.³ This discrepancy again suggests that women may not be aware of the potential harms of e-cigarettes in pregnancy, which is not surprising considering that prenatal care clinicians often are not appropriately screening or counseling regarding e-cigarette use.⁴

We must specifically ask about vaping and e-cigarette use as part of our prenatal care and counsel women that the use of e-cigarettes is not a safer alternative to cigarette smoking. I urge patients who have switched to e-cigarettes as a means of smoking cessation or as a choice they perceive to be safer to work together with me to find another way to reduce potential harm to their baby.

References

1. J Addict Med. 2015 Jul-Aug;9(4):266-72.

2. Obstet Gynecol Surv. 2018 Sep;73(9):544-9.

3. JAMA Pediatr. 2019 Jun 1;173(6):600-2.

4. Am J Obstet Gynecol. 2014 Dec;211(6):695.e1-7.

We know that the environment significantly impacts our health. People who live in areas prone to industrial waste, poor air or water quality, and crime have higher risks for cardiovascular disease, severe asthma, and stress-induced illnesses. Children who grow up under these conditions can experience a failure to thrive.

As ob.gyns., we also recognize that the intrauterine environment plays a key role in influencing embryonic and fetal development. For this reason, we counsel our pregnant patients to eat well-balanced diets, drink healthy amounts of water, get plenty of rest, and incorporate physical activity into their daily routines. Indeed, the seminal work by Sir David Barker demonstrated that the roots of chronic diseases – including hypertension, stroke, and type 2 diabetes – begin in utero. We truly are where we live – from before birth up through adulthood.

Because the womb environment, where we spend the first critical 9 months of life, dramatically affects our lifelong health, we advise against the use of certain medications and other substances during pregnancy. Some of these recommendations seem clear-cut: Don’t smoke and significantly reduce or abstain from alcohol consumption; illicit drugs – such as cocaine or heroin – should never be used. However, gray areas exist. For example, although anticonvulsants carry higher risks for congenital malformations, patients who experience seizures may need to continue taking antiepileptic drugs during pregnancy, especially those with long safety records.

One of the newer challenges the medical community in general must face is the broadened use and wider societal acceptance of cannabis. Currently legal in 33 U.S. states and Washington, D.C., medical marijuana now is viewed as another legitimate tool in the health care arsenal, rather than the off-limits, off-label substance it was less than a generation ago.

Although proponents may tout the health benefits of cannabis and related products like cannabidiol, it remains unclear what the long-term effects of routine use may have on development, especially fetal development. Research in this area still is relatively new, but data indicate that more harm than good may come from cannabis exposure during pregnancy. However, how we as ob.gyns. navigate conversations with our patients around substance use remains crucial to our delivery of the best possible prenatal care.

We have invited Katrina S. Mark, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, to examine use of cannabis in pregnancy and the need for maintaining trust in the patient-practitioner relationship when discussing substance use during prenatal counseling.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.

We know that the environment significantly impacts our health. People who live in areas prone to industrial waste, poor air or water quality, and crime have higher risks for cardiovascular disease, severe asthma, and stress-induced illnesses. Children who grow up under these conditions can experience a failure to thrive.

As ob.gyns., we also recognize that the intrauterine environment plays a key role in influencing embryonic and fetal development. For this reason, we counsel our pregnant patients to eat well-balanced diets, drink healthy amounts of water, get plenty of rest, and incorporate physical activity into their daily routines. Indeed, the seminal work by Sir David Barker demonstrated that the roots of chronic diseases – including hypertension, stroke, and type 2 diabetes – begin in utero. We truly are where we live – from before birth up through adulthood.

Because the womb environment, where we spend the first critical 9 months of life, dramatically affects our lifelong health, we advise against the use of certain medications and other substances during pregnancy. Some of these recommendations seem clear-cut: Don’t smoke and significantly reduce or abstain from alcohol consumption; illicit drugs – such as cocaine or heroin – should never be used. However, gray areas exist. For example, although anticonvulsants carry higher risks for congenital malformations, patients who experience seizures may need to continue taking antiepileptic drugs during pregnancy, especially those with long safety records.

One of the newer challenges the medical community in general must face is the broadened use and wider societal acceptance of cannabis. Currently legal in 33 U.S. states and Washington, D.C., medical marijuana now is viewed as another legitimate tool in the health care arsenal, rather than the off-limits, off-label substance it was less than a generation ago.

Although proponents may tout the health benefits of cannabis and related products like cannabidiol, it remains unclear what the long-term effects of routine use may have on development, especially fetal development. Research in this area still is relatively new, but data indicate that more harm than good may come from cannabis exposure during pregnancy. However, how we as ob.gyns. navigate conversations with our patients around substance use remains crucial to our delivery of the best possible prenatal care.

We have invited Katrina S. Mark, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, to examine use of cannabis in pregnancy and the need for maintaining trust in the patient-practitioner relationship when discussing substance use during prenatal counseling.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.

We know that the environment significantly impacts our health. People who live in areas prone to industrial waste, poor air or water quality, and crime have higher risks for cardiovascular disease, severe asthma, and stress-induced illnesses. Children who grow up under these conditions can experience a failure to thrive.

As ob.gyns., we also recognize that the intrauterine environment plays a key role in influencing embryonic and fetal development. For this reason, we counsel our pregnant patients to eat well-balanced diets, drink healthy amounts of water, get plenty of rest, and incorporate physical activity into their daily routines. Indeed, the seminal work by Sir David Barker demonstrated that the roots of chronic diseases – including hypertension, stroke, and type 2 diabetes – begin in utero. We truly are where we live – from before birth up through adulthood.

Because the womb environment, where we spend the first critical 9 months of life, dramatically affects our lifelong health, we advise against the use of certain medications and other substances during pregnancy. Some of these recommendations seem clear-cut: Don’t smoke and significantly reduce or abstain from alcohol consumption; illicit drugs – such as cocaine or heroin – should never be used. However, gray areas exist. For example, although anticonvulsants carry higher risks for congenital malformations, patients who experience seizures may need to continue taking antiepileptic drugs during pregnancy, especially those with long safety records.

One of the newer challenges the medical community in general must face is the broadened use and wider societal acceptance of cannabis. Currently legal in 33 U.S. states and Washington, D.C., medical marijuana now is viewed as another legitimate tool in the health care arsenal, rather than the off-limits, off-label substance it was less than a generation ago.

Although proponents may tout the health benefits of cannabis and related products like cannabidiol, it remains unclear what the long-term effects of routine use may have on development, especially fetal development. Research in this area still is relatively new, but data indicate that more harm than good may come from cannabis exposure during pregnancy. However, how we as ob.gyns. navigate conversations with our patients around substance use remains crucial to our delivery of the best possible prenatal care.

We have invited Katrina S. Mark, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, to examine use of cannabis in pregnancy and the need for maintaining trust in the patient-practitioner relationship when discussing substance use during prenatal counseling.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.

A flurry of research papers published this year has simultaneously documented a rise in the use of cannabis during pregnancy and offered more data about its potential harms. This confluence of findings is concerning and highlights the importance of screening our patients for cannabis use and engaging with them in a way in which we can maintain their trust and their commitment to prenatal care.

Stuart Jenner/Thinkstock

A retrospective cohort study involving 661,617 women in Ontario found a significant association between self-reported cannabis use in pregnancy and an increased risk of preterm birth (relative risk, 1.41), as well as a greater likelihood of small-for-gestational-age babies (RR, 1.53), placental abruption (RR, 1.72), and transfer to neonatal intensive care (RR, 1.40).¹ The study, reported in JAMA in July 2019, carefully matched users with nonusers who had the same characteristics – for example, tobacco use or not.

This new information builds upon other meta-analyses that have demonstrated a decrease in birth weight and greater admittance to the neonatal ICU associated with cannabis use in pregnancy – and it supplements what some research suggests about long-term neurologic development and a potentially increased risk of attention and behavioral problems. Other outcomes that have been noted in long-term neurologic studies of children who were exposed to cannabis in utero include impaired visual acuity, verbal reasoning and comprehension, and short-term memory.²

Increases in use were recently documented in two studies. One, an analysis of data from the National Survey on Drug Use and Health (NSDUH) published in JAMA in June 2019, showed that, between 2002-2003 and 2016-2017, the use of cannabis “in the past month” increased from 3.4% to 7.0% among pregnant women overall, and from 6% to 12% during the first trimester.³

The use of cannabis on a daily or near-daily basis, moreover, increased from 0.9% to 3% among pregnant women overall and from 2% to 5% during the first trimester. The data were collected during face-to-face interviews and were adjusted for age, race/ethnicity, and family income.

In the second study – a cross-sectional study of 367,403 pregnancies among women who filled out a questionnaire on cannabis use during standard prenatal care at Kaiser Permanente Northern California – the adjusted prevalence of use in the year before pregnancy increased from 7% in 2009 to 13% in 2017, and the adjusted prevalence during pregnancy increased from 2% to 3%.⁴

As in the NSDUH analysis, daily use increased most rapidly (compared with weekly or monthly) such that, by 2017, 25% of those who reported using cannabis in the year before pregnancy – and 21% of those who used cannabis during pregnancy – were daily users. It is notable that Kaiser’s population is diverse in all respects, and that the annual relative rates of increase in cannabis use before and during pregnancy (at each level of frequency) were consistent across racial/ethnic and household income groups.

It’s also worth noting that, in earlier research covering a similar time period (2009-2016), the investigators found significant increases in use via urine toxicology testing that occurs at the first prenatal visit at Kaiser. The increase found through questionnaires, therefore, reflects more than a greater willingness to self-report.

Choosing a screening tool

Universal prenatal substance use screening is recommended by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention, but we don’t have any specific recommendations on what this means. Who should be screening, and what should that screening look like? Should we use a biologic screen, a standardized screening tool, or simply ask patients whether they use illicit substances?

Screening tools seem advantageous in that they are low cost, noninvasive, potentially comprehensive, and not subject to false-positive results as biologic screens can be – but which tool or tools are best? There are several validated screening tools that can be used outside of pregnancy to determine an individual’s use of illicit substances and whether or not that use is problematic, but previous studies have not used biologic markers to validate substance use screeners in pregnancy. Nor have studies compared screeners in pregnancy.

In our prenatal population in Baltimore, we have not been getting the answers we want using various nonvalidated screening tools. Approximately 30% of patients are positive for cannabis by urine screen, but only half tell us about their use.

Through research in our two prenatal care practices (one serving mostly privately insured and the other serving primarily Medicaid-eligible patients), we assessed both the accuracy and the acceptability of three substance use screening tools that are brief and that have been validated (for the general population) by the World Health Organization for screening of multiple substances: the 4P’s Plus (Parents, Partner, Past, and Pregnancy), the National Institute on Drug Abuse Quick Screen–ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile–Pregnancy) scale.

In one study, published in May 2019 in Obstetrics & Gynecology, we recruited 500 pregnant women and administered these three tests to each of them.⁵ We then compared results with those of urine and hair drug testing, and checked the test-retest reliability of each test by readministering them (albeit by telephone) a week later. Although hair testing is not an indicator of current substance use, we used it to validate the screening tools on less-recent use.

The tests with the highest sensitivity and negative predictive values – the qualities we most want for screening – were the SURP-P and the 4P’s Plus (sensitivity of 92.4% and 90.2%, respectively). Overall they were highly sensitive screening tools across all trimesters, races, and age groups, making them more ideal screening tests than the NIDA Quick Screen–ASSIST.

Of the two tests, the 4P’s Plus screening tool was the one preferred by staff from both practices. In a companion qualitative study, we conducted focus-group discussions with 40 practice staff who were responsible for administering or overseeing patient screening.⁶ The staff, who were unaware of the sensitivity findings, were asked what they thought about the acceptability to patients of each of the three tools and their usability in practice.

Most of the participating staff preferred the 4P’s Plus screening tool for several reasons: It is easy to understand, is brief and to the point, and it has nonjudgmental language and tone. The screener first asks the patient about her parents’ and her partner’s use of alcohol and drugs, and then asks the patient about her own use of alcohol and tobacco. Affirmative responses to these questions lead to additional questions.

The premise is that one’s genetics, history, and current exposures – as well as one’s own use of tobacco and alcohol – are significantly associated with the use of illicit substances. If the patient reports no parental history or partner usage, and has never drank or smoked before, it’s extremely unlikely that she is using other drugs. The progression of questions does indeed seem less judgmental than immediately asking: “Do you use drugs?”

For us, the insight from this staff perception study combined with the findings on accuracy mean that the 4P’s Plus may be the most useful and acceptable screening tool for routine use in prenatal care.

Talking with our patients

The increase in the use of cannabis before and after pregnancy parallels the movement toward state legalization and decriminalization. Historically, clinicians often have relied on illegality as their main focus of counseling when giving recommendations for cessation and abstinence in pregnancy.² This approach not only leads to punitive counseling, which can fracture the doctor-patient relationship, but increasingly it is no longer valid. In our changing legal climate, we need to provide medically based counseling and be very clear with our patients that legalization does not equate to safety.

It is important that we neither minimize nor overstate the risks. The evidence base for adverse birth outcomes of cannabis use in pregnancy is quite robust, but the associations can be subtle and are moderated by other behaviors and environmental factors that continue to challenge researchers.

As with alcohol, there likely are dose-or trimester-dependent differences in perinatal outcomes, and it’s quite possible that different cannabis products and routes of consumption have different effects. At this point, however, we don’t know the full story, nor do we know the extent to which the literature is biased toward positive correlations – the reporting of adverse effects – compared with negative findings. It is our job as medical care providers to be comfortable in that gray area and to still counsel patients on what we do know, providing the best-possible medical advice based on the information available to us.

In talking with patients, I explain that cannabis may cause a spectrum of problems and that there certainly are risks. I also tell them that we’re uncertain about the conditions and magnitude of that risk and that some babies who are exposed to cannabis in utero may have no perceivable consequences. Such honesty is important for maintaining trust, especially as some patients may see friends and relatives who also are cannabis users have normal pregnancy outcomes.

Much of my concern about cannabis in pregnancy centers on its effect on the developing brain and on long-term neurologic development. I share this with patients – I tell them that cannabis crosses the placenta and may well affect their baby’s brain as it is developing. I explain that I do not know whether this effect would be big or small, but that it’s not a chance I’m willing to take for their baby.

It is also important to educate patients that cannabis products are untested and unregulated and that they may be contaminated with heavy metals, pesticides, and other toxins that may be harmful to themselves and their babies. Patients also should know that the potency of cannabis has been dramatically increasing; research shows that the tetrahydrocannabinol – the psychoactive component – concentration has tripled over the past 2 decades.⁷

Research tells us that women who use illicit drugs and alcohol categorically engage in some form of harm reduction once they learn they are pregnant, and the same is true for cannabis. This is seen in dramatically different rates of first- and third-trimester use in the new analysis of NSDUH data; third-trimester use is approximately halved.

Some women will not be able to discontinue use, however, or they may try to quit and fail in their attempts. As we should with substance use more broadly, we must meet patients where they are, view cannabis use as a chronic medical problem, offer our assistance in helping them reduce harms of their use, and understand that quitting is a process.

Screening for mental health disorders and trauma is, of course, especially important in patients who use cannabis and other substances recreationally. In cases of medical marijuana usage, I recommend, as ACOG and other have done, that we discuss the risks and benefits of continuing cannabis versus shifting to alternative medications if options exist.

In any case, we must guard against cannabis use dominating all conversations throughout our prenatal care. All patients should be welcomed, congratulated on their pregnancy and on coming for prenatal care, and engaged in the overall process of optimizing their health and the health of their baby. Like any other health issue during pregnancy, cannabis use needs to be screened for and treated in an evidence-based manner, but it does not define the trajectory or success of a woman’s pregnancy or her ability to be a successful parent.

Dr. Mark is associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.

References

1. JAMA. 2019 Jul 9;322(2):145-52.

2. Preventive Medicine 2017 May 18;104:46-9.

3. JAMA. 2019 Jul 9;322(2):167-9.

4. JAMA Netw Open. 2019 Jul 3;2(7):e196471.

5. Obstet Gynecol. 2019 May;133(5):952-61.

6. J. Addict Med. 2019 May 10. doi: 10.1097/ADM.0000000000000543.

7. Biol Psychiatry. 2016 Apr 1;79(7):613-9.

A flurry of research papers published this year has simultaneously documented a rise in the use of cannabis during pregnancy and offered more data about its potential harms. This confluence of findings is concerning and highlights the importance of screening our patients for cannabis use and engaging with them in a way in which we can maintain their trust and their commitment to prenatal care.

Stuart Jenner/Thinkstock

A retrospective cohort study involving 661,617 women in Ontario found a significant association between self-reported cannabis use in pregnancy and an increased risk of preterm birth (relative risk, 1.41), as well as a greater likelihood of small-for-gestational-age babies (RR, 1.53), placental abruption (RR, 1.72), and transfer to neonatal intensive care (RR, 1.40).¹ The study, reported in JAMA in July 2019, carefully matched users with nonusers who had the same characteristics – for example, tobacco use or not.

This new information builds upon other meta-analyses that have demonstrated a decrease in birth weight and greater admittance to the neonatal ICU associated with cannabis use in pregnancy – and it supplements what some research suggests about long-term neurologic development and a potentially increased risk of attention and behavioral problems. Other outcomes that have been noted in long-term neurologic studies of children who were exposed to cannabis in utero include impaired visual acuity, verbal reasoning and comprehension, and short-term memory.²

Increases in use were recently documented in two studies. One, an analysis of data from the National Survey on Drug Use and Health (NSDUH) published in JAMA in June 2019, showed that, between 2002-2003 and 2016-2017, the use of cannabis “in the past month” increased from 3.4% to 7.0% among pregnant women overall, and from 6% to 12% during the first trimester.³

The use of cannabis on a daily or near-daily basis, moreover, increased from 0.9% to 3% among pregnant women overall and from 2% to 5% during the first trimester. The data were collected during face-to-face interviews and were adjusted for age, race/ethnicity, and family income.

In the second study – a cross-sectional study of 367,403 pregnancies among women who filled out a questionnaire on cannabis use during standard prenatal care at Kaiser Permanente Northern California – the adjusted prevalence of use in the year before pregnancy increased from 7% in 2009 to 13% in 2017, and the adjusted prevalence during pregnancy increased from 2% to 3%.⁴

As in the NSDUH analysis, daily use increased most rapidly (compared with weekly or monthly) such that, by 2017, 25% of those who reported using cannabis in the year before pregnancy – and 21% of those who used cannabis during pregnancy – were daily users. It is notable that Kaiser’s population is diverse in all respects, and that the annual relative rates of increase in cannabis use before and during pregnancy (at each level of frequency) were consistent across racial/ethnic and household income groups.

It’s also worth noting that, in earlier research covering a similar time period (2009-2016), the investigators found significant increases in use via urine toxicology testing that occurs at the first prenatal visit at Kaiser. The increase found through questionnaires, therefore, reflects more than a greater willingness to self-report.

Choosing a screening tool

Universal prenatal substance use screening is recommended by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention, but we don’t have any specific recommendations on what this means. Who should be screening, and what should that screening look like? Should we use a biologic screen, a standardized screening tool, or simply ask patients whether they use illicit substances?

Screening tools seem advantageous in that they are low cost, noninvasive, potentially comprehensive, and not subject to false-positive results as biologic screens can be – but which tool or tools are best? There are several validated screening tools that can be used outside of pregnancy to determine an individual’s use of illicit substances and whether or not that use is problematic, but previous studies have not used biologic markers to validate substance use screeners in pregnancy. Nor have studies compared screeners in pregnancy.

In our prenatal population in Baltimore, we have not been getting the answers we want using various nonvalidated screening tools. Approximately 30% of patients are positive for cannabis by urine screen, but only half tell us about their use.

Through research in our two prenatal care practices (one serving mostly privately insured and the other serving primarily Medicaid-eligible patients), we assessed both the accuracy and the acceptability of three substance use screening tools that are brief and that have been validated (for the general population) by the World Health Organization for screening of multiple substances: the 4P’s Plus (Parents, Partner, Past, and Pregnancy), the National Institute on Drug Abuse Quick Screen–ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile–Pregnancy) scale.

In one study, published in May 2019 in Obstetrics & Gynecology, we recruited 500 pregnant women and administered these three tests to each of them.⁵ We then compared results with those of urine and hair drug testing, and checked the test-retest reliability of each test by readministering them (albeit by telephone) a week later. Although hair testing is not an indicator of current substance use, we used it to validate the screening tools on less-recent use.

The tests with the highest sensitivity and negative predictive values – the qualities we most want for screening – were the SURP-P and the 4P’s Plus (sensitivity of 92.4% and 90.2%, respectively). Overall they were highly sensitive screening tools across all trimesters, races, and age groups, making them more ideal screening tests than the NIDA Quick Screen–ASSIST.

Of the two tests, the 4P’s Plus screening tool was the one preferred by staff from both practices. In a companion qualitative study, we conducted focus-group discussions with 40 practice staff who were responsible for administering or overseeing patient screening.⁶ The staff, who were unaware of the sensitivity findings, were asked what they thought about the acceptability to patients of each of the three tools and their usability in practice.

Most of the participating staff preferred the 4P’s Plus screening tool for several reasons: It is easy to understand, is brief and to the point, and it has nonjudgmental language and tone. The screener first asks the patient about her parents’ and her partner’s use of alcohol and drugs, and then asks the patient about her own use of alcohol and tobacco. Affirmative responses to these questions lead to additional questions.

The premise is that one’s genetics, history, and current exposures – as well as one’s own use of tobacco and alcohol – are significantly associated with the use of illicit substances. If the patient reports no parental history or partner usage, and has never drank or smoked before, it’s extremely unlikely that she is using other drugs. The progression of questions does indeed seem less judgmental than immediately asking: “Do you use drugs?”

For us, the insight from this staff perception study combined with the findings on accuracy mean that the 4P’s Plus may be the most useful and acceptable screening tool for routine use in prenatal care.

Talking with our patients

The increase in the use of cannabis before and after pregnancy parallels the movement toward state legalization and decriminalization. Historically, clinicians often have relied on illegality as their main focus of counseling when giving recommendations for cessation and abstinence in pregnancy.² This approach not only leads to punitive counseling, which can fracture the doctor-patient relationship, but increasingly it is no longer valid. In our changing legal climate, we need to provide medically based counseling and be very clear with our patients that legalization does not equate to safety.

It is important that we neither minimize nor overstate the risks. The evidence base for adverse birth outcomes of cannabis use in pregnancy is quite robust, but the associations can be subtle and are moderated by other behaviors and environmental factors that continue to challenge researchers.

As with alcohol, there likely are dose-or trimester-dependent differences in perinatal outcomes, and it’s quite possible that different cannabis products and routes of consumption have different effects. At this point, however, we don’t know the full story, nor do we know the extent to which the literature is biased toward positive correlations – the reporting of adverse effects – compared with negative findings. It is our job as medical care providers to be comfortable in that gray area and to still counsel patients on what we do know, providing the best-possible medical advice based on the information available to us.

In talking with patients, I explain that cannabis may cause a spectrum of problems and that there certainly are risks. I also tell them that we’re uncertain about the conditions and magnitude of that risk and that some babies who are exposed to cannabis in utero may have no perceivable consequences. Such honesty is important for maintaining trust, especially as some patients may see friends and relatives who also are cannabis users have normal pregnancy outcomes.

Much of my concern about cannabis in pregnancy centers on its effect on the developing brain and on long-term neurologic development. I share this with patients – I tell them that cannabis crosses the placenta and may well affect their baby’s brain as it is developing. I explain that I do not know whether this effect would be big or small, but that it’s not a chance I’m willing to take for their baby.

It is also important to educate patients that cannabis products are untested and unregulated and that they may be contaminated with heavy metals, pesticides, and other toxins that may be harmful to themselves and their babies. Patients also should know that the potency of cannabis has been dramatically increasing; research shows that the tetrahydrocannabinol – the psychoactive component – concentration has tripled over the past 2 decades.⁷

Research tells us that women who use illicit drugs and alcohol categorically engage in some form of harm reduction once they learn they are pregnant, and the same is true for cannabis. This is seen in dramatically different rates of first- and third-trimester use in the new analysis of NSDUH data; third-trimester use is approximately halved.

Some women will not be able to discontinue use, however, or they may try to quit and fail in their attempts. As we should with substance use more broadly, we must meet patients where they are, view cannabis use as a chronic medical problem, offer our assistance in helping them reduce harms of their use, and understand that quitting is a process.

Screening for mental health disorders and trauma is, of course, especially important in patients who use cannabis and other substances recreationally. In cases of medical marijuana usage, I recommend, as ACOG and other have done, that we discuss the risks and benefits of continuing cannabis versus shifting to alternative medications if options exist.

In any case, we must guard against cannabis use dominating all conversations throughout our prenatal care. All patients should be welcomed, congratulated on their pregnancy and on coming for prenatal care, and engaged in the overall process of optimizing their health and the health of their baby. Like any other health issue during pregnancy, cannabis use needs to be screened for and treated in an evidence-based manner, but it does not define the trajectory or success of a woman’s pregnancy or her ability to be a successful parent.

Dr. Mark is associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.

References

1. JAMA. 2019 Jul 9;322(2):145-52.

2. Preventive Medicine 2017 May 18;104:46-9.

3. JAMA. 2019 Jul 9;322(2):167-9.

4. JAMA Netw Open. 2019 Jul 3;2(7):e196471.

5. Obstet Gynecol. 2019 May;133(5):952-61.

6. J. Addict Med. 2019 May 10. doi: 10.1097/ADM.0000000000000543.

7. Biol Psychiatry. 2016 Apr 1;79(7):613-9.

A flurry of research papers published this year has simultaneously documented a rise in the use of cannabis during pregnancy and offered more data about its potential harms. This confluence of findings is concerning and highlights the importance of screening our patients for cannabis use and engaging with them in a way in which we can maintain their trust and their commitment to prenatal care.

Stuart Jenner/Thinkstock

A retrospective cohort study involving 661,617 women in Ontario found a significant association between self-reported cannabis use in pregnancy and an increased risk of preterm birth (relative risk, 1.41), as well as a greater likelihood of small-for-gestational-age babies (RR, 1.53), placental abruption (RR, 1.72), and transfer to neonatal intensive care (RR, 1.40).¹ The study, reported in JAMA in July 2019, carefully matched users with nonusers who had the same characteristics – for example, tobacco use or not.

This new information builds upon other meta-analyses that have demonstrated a decrease in birth weight and greater admittance to the neonatal ICU associated with cannabis use in pregnancy – and it supplements what some research suggests about long-term neurologic development and a potentially increased risk of attention and behavioral problems. Other outcomes that have been noted in long-term neurologic studies of children who were exposed to cannabis in utero include impaired visual acuity, verbal reasoning and comprehension, and short-term memory.²

Increases in use were recently documented in two studies. One, an analysis of data from the National Survey on Drug Use and Health (NSDUH) published in JAMA in June 2019, showed that, between 2002-2003 and 2016-2017, the use of cannabis “in the past month” increased from 3.4% to 7.0% among pregnant women overall, and from 6% to 12% during the first trimester.³

The use of cannabis on a daily or near-daily basis, moreover, increased from 0.9% to 3% among pregnant women overall and from 2% to 5% during the first trimester. The data were collected during face-to-face interviews and were adjusted for age, race/ethnicity, and family income.

In the second study – a cross-sectional study of 367,403 pregnancies among women who filled out a questionnaire on cannabis use during standard prenatal care at Kaiser Permanente Northern California – the adjusted prevalence of use in the year before pregnancy increased from 7% in 2009 to 13% in 2017, and the adjusted prevalence during pregnancy increased from 2% to 3%.⁴

As in the NSDUH analysis, daily use increased most rapidly (compared with weekly or monthly) such that, by 2017, 25% of those who reported using cannabis in the year before pregnancy – and 21% of those who used cannabis during pregnancy – were daily users. It is notable that Kaiser’s population is diverse in all respects, and that the annual relative rates of increase in cannabis use before and during pregnancy (at each level of frequency) were consistent across racial/ethnic and household income groups.

It’s also worth noting that, in earlier research covering a similar time period (2009-2016), the investigators found significant increases in use via urine toxicology testing that occurs at the first prenatal visit at Kaiser. The increase found through questionnaires, therefore, reflects more than a greater willingness to self-report.

Choosing a screening tool

Universal prenatal substance use screening is recommended by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention, but we don’t have any specific recommendations on what this means. Who should be screening, and what should that screening look like? Should we use a biologic screen, a standardized screening tool, or simply ask patients whether they use illicit substances?

Screening tools seem advantageous in that they are low cost, noninvasive, potentially comprehensive, and not subject to false-positive results as biologic screens can be – but which tool or tools are best? There are several validated screening tools that can be used outside of pregnancy to determine an individual’s use of illicit substances and whether or not that use is problematic, but previous studies have not used biologic markers to validate substance use screeners in pregnancy. Nor have studies compared screeners in pregnancy.

In our prenatal population in Baltimore, we have not been getting the answers we want using various nonvalidated screening tools. Approximately 30% of patients are positive for cannabis by urine screen, but only half tell us about their use.

Through research in our two prenatal care practices (one serving mostly privately insured and the other serving primarily Medicaid-eligible patients), we assessed both the accuracy and the acceptability of three substance use screening tools that are brief and that have been validated (for the general population) by the World Health Organization for screening of multiple substances: the 4P’s Plus (Parents, Partner, Past, and Pregnancy), the National Institute on Drug Abuse Quick Screen–ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile–Pregnancy) scale.

In one study, published in May 2019 in Obstetrics & Gynecology, we recruited 500 pregnant women and administered these three tests to each of them.⁵ We then compared results with those of urine and hair drug testing, and checked the test-retest reliability of each test by readministering them (albeit by telephone) a week later. Although hair testing is not an indicator of current substance use, we used it to validate the screening tools on less-recent use.

The tests with the highest sensitivity and negative predictive values – the qualities we most want for screening – were the SURP-P and the 4P’s Plus (sensitivity of 92.4% and 90.2%, respectively). Overall they were highly sensitive screening tools across all trimesters, races, and age groups, making them more ideal screening tests than the NIDA Quick Screen–ASSIST.

Of the two tests, the 4P’s Plus screening tool was the one preferred by staff from both practices. In a companion qualitative study, we conducted focus-group discussions with 40 practice staff who were responsible for administering or overseeing patient screening.⁶ The staff, who were unaware of the sensitivity findings, were asked what they thought about the acceptability to patients of each of the three tools and their usability in practice.

Most of the participating staff preferred the 4P’s Plus screening tool for several reasons: It is easy to understand, is brief and to the point, and it has nonjudgmental language and tone. The screener first asks the patient about her parents’ and her partner’s use of alcohol and drugs, and then asks the patient about her own use of alcohol and tobacco. Affirmative responses to these questions lead to additional questions.

The premise is that one’s genetics, history, and current exposures – as well as one’s own use of tobacco and alcohol – are significantly associated with the use of illicit substances. If the patient reports no parental history or partner usage, and has never drank or smoked before, it’s extremely unlikely that she is using other drugs. The progression of questions does indeed seem less judgmental than immediately asking: “Do you use drugs?”

For us, the insight from this staff perception study combined with the findings on accuracy mean that the 4P’s Plus may be the most useful and acceptable screening tool for routine use in prenatal care.

Talking with our patients

The increase in the use of cannabis before and after pregnancy parallels the movement toward state legalization and decriminalization. Historically, clinicians often have relied on illegality as their main focus of counseling when giving recommendations for cessation and abstinence in pregnancy.² This approach not only leads to punitive counseling, which can fracture the doctor-patient relationship, but increasingly it is no longer valid. In our changing legal climate, we need to provide medically based counseling and be very clear with our patients that legalization does not equate to safety.

It is important that we neither minimize nor overstate the risks. The evidence base for adverse birth outcomes of cannabis use in pregnancy is quite robust, but the associations can be subtle and are moderated by other behaviors and environmental factors that continue to challenge researchers.

As with alcohol, there likely are dose-or trimester-dependent differences in perinatal outcomes, and it’s quite possible that different cannabis products and routes of consumption have different effects. At this point, however, we don’t know the full story, nor do we know the extent to which the literature is biased toward positive correlations – the reporting of adverse effects – compared with negative findings. It is our job as medical care providers to be comfortable in that gray area and to still counsel patients on what we do know, providing the best-possible medical advice based on the information available to us.

In talking with patients, I explain that cannabis may cause a spectrum of problems and that there certainly are risks. I also tell them that we’re uncertain about the conditions and magnitude of that risk and that some babies who are exposed to cannabis in utero may have no perceivable consequences. Such honesty is important for maintaining trust, especially as some patients may see friends and relatives who also are cannabis users have normal pregnancy outcomes.

Much of my concern about cannabis in pregnancy centers on its effect on the developing brain and on long-term neurologic development. I share this with patients – I tell them that cannabis crosses the placenta and may well affect their baby’s brain as it is developing. I explain that I do not know whether this effect would be big or small, but that it’s not a chance I’m willing to take for their baby.

It is also important to educate patients that cannabis products are untested and unregulated and that they may be contaminated with heavy metals, pesticides, and other toxins that may be harmful to themselves and their babies. Patients also should know that the potency of cannabis has been dramatically increasing; research shows that the tetrahydrocannabinol – the psychoactive component – concentration has tripled over the past 2 decades.⁷

Research tells us that women who use illicit drugs and alcohol categorically engage in some form of harm reduction once they learn they are pregnant, and the same is true for cannabis. This is seen in dramatically different rates of first- and third-trimester use in the new analysis of NSDUH data; third-trimester use is approximately halved.

Some women will not be able to discontinue use, however, or they may try to quit and fail in their attempts. As we should with substance use more broadly, we must meet patients where they are, view cannabis use as a chronic medical problem, offer our assistance in helping them reduce harms of their use, and understand that quitting is a process.

Screening for mental health disorders and trauma is, of course, especially important in patients who use cannabis and other substances recreationally. In cases of medical marijuana usage, I recommend, as ACOG and other have done, that we discuss the risks and benefits of continuing cannabis versus shifting to alternative medications if options exist.

In any case, we must guard against cannabis use dominating all conversations throughout our prenatal care. All patients should be welcomed, congratulated on their pregnancy and on coming for prenatal care, and engaged in the overall process of optimizing their health and the health of their baby. Like any other health issue during pregnancy, cannabis use needs to be screened for and treated in an evidence-based manner, but it does not define the trajectory or success of a woman’s pregnancy or her ability to be a successful parent.

Dr. Mark is associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.

References

1. JAMA. 2019 Jul 9;322(2):145-52.

2. Preventive Medicine 2017 May 18;104:46-9.

3. JAMA. 2019 Jul 9;322(2):167-9.

4. JAMA Netw Open. 2019 Jul 3;2(7):e196471.

5. Obstet Gynecol. 2019 May;133(5):952-61.

6. J. Addict Med. 2019 May 10. doi: 10.1097/ADM.0000000000000543.

7. Biol Psychiatry. 2016 Apr 1;79(7):613-9.

Antifungal prophylaxis with caspofungin led to a lower incidence of invasive fungal disease, compared with fluconazole, in children and young adults with acute myeloid leukemia (AML), according to new study findings.

National Institutes of Health/Wikimedia Commons/Public Domain

The results suggest caspofungin may be an appropriate prophylactic strategy to prevent invasive fungal disease in younger patients with newly diagnosed AML, reported Brian T. Fisher, DO, of the University of Pennsylvania, Philadelphia, and colleagues. The study was published in JAMA.

The randomized, open-label study included 517 children, adolescents, and young adults with de novo, relapsed, or secondary AML. Study patients received treatment in 115 centers throughout United States and Canada. The median age of patients in the study was 9 years (range, 0-26 years); 56% were male and approximately 69% were white.

Study subjects were randomly assigned to receive antifungal prophylaxis with 70 mg/m² (maximum dose 70 mg/day) of intravenous caspofungin on day 1, followed by 50 mg/m² per day (maximum dose 50 mg/day) thereafter, or age-dosed intravenous or oral fluconazole.

Prophylactic therapy was initiated 24-72 hours after the completion of each chemotherapy cycle, and was maintained until the end of the neutropenic period following each cycle.

At 5-month follow-up, the cumulative incidence rate of probable or proven invasive fungal disease was 3.1% (95% confidence interval, 1.3%-7.0%) in the caspofungin arm, compared with 7.2% (95% CI, 4.4%-11.8%) in the fluconazole arm (overall P = .03).

In addition, the 5-month cumulative incidence rate of probable or proven invasive aspergillosis infection was 0.5% (95%CI, 0.1%-3.5%) in patients who received caspofungin, compared with 3.1% (95% CI, 1.4%-6.9%) in patients who received fluconazole (overall P = .046).

“No statistically significant differences in empirical antifungal therapy or 2-year overall survival were observed,” they reported.

With respect to safety, the most frequently reported adverse events were hypokalemia (22 events in the caspofungin arm vs. 13 in the fluconazole arm), respiratory failure (6 events in the caspofungin arm vs. 9 in the fluconazole arm), and elevated alanine transaminase (4 events in the caspofungin arm vs. 8 in the fluconazole arm).

The researchers acknowledged a key limitation of the study was the short duration of follow-up. As a result, the precision of some comparative measures may have been reduced.

The National Cancer Institute funded the study. The authors reported financial affiliations with Astellas, Celgene, Leadiant Biosciences, Merck, Nabriva Therapeutics, Novartis, Pfizer, Shire, and T2 Biosystems.

SOURCE: Fisher BT et al. JAMA. 2019;322(17):1673-81.

Antifungal prophylaxis with caspofungin led to a lower incidence of invasive fungal disease, compared with fluconazole, in children and young adults with acute myeloid leukemia (AML), according to new study findings.

National Institutes of Health/Wikimedia Commons/Public Domain

The results suggest caspofungin may be an appropriate prophylactic strategy to prevent invasive fungal disease in younger patients with newly diagnosed AML, reported Brian T. Fisher, DO, of the University of Pennsylvania, Philadelphia, and colleagues. The study was published in JAMA.

The randomized, open-label study included 517 children, adolescents, and young adults with de novo, relapsed, or secondary AML. Study patients received treatment in 115 centers throughout United States and Canada. The median age of patients in the study was 9 years (range, 0-26 years); 56% were male and approximately 69% were white.

Study subjects were randomly assigned to receive antifungal prophylaxis with 70 mg/m² (maximum dose 70 mg/day) of intravenous caspofungin on day 1, followed by 50 mg/m² per day (maximum dose 50 mg/day) thereafter, or age-dosed intravenous or oral fluconazole.

Prophylactic therapy was initiated 24-72 hours after the completion of each chemotherapy cycle, and was maintained until the end of the neutropenic period following each cycle.

At 5-month follow-up, the cumulative incidence rate of probable or proven invasive fungal disease was 3.1% (95% confidence interval, 1.3%-7.0%) in the caspofungin arm, compared with 7.2% (95% CI, 4.4%-11.8%) in the fluconazole arm (overall P = .03).

In addition, the 5-month cumulative incidence rate of probable or proven invasive aspergillosis infection was 0.5% (95%CI, 0.1%-3.5%) in patients who received caspofungin, compared with 3.1% (95% CI, 1.4%-6.9%) in patients who received fluconazole (overall P = .046).

“No statistically significant differences in empirical antifungal therapy or 2-year overall survival were observed,” they reported.

With respect to safety, the most frequently reported adverse events were hypokalemia (22 events in the caspofungin arm vs. 13 in the fluconazole arm), respiratory failure (6 events in the caspofungin arm vs. 9 in the fluconazole arm), and elevated alanine transaminase (4 events in the caspofungin arm vs. 8 in the fluconazole arm).

The researchers acknowledged a key limitation of the study was the short duration of follow-up. As a result, the precision of some comparative measures may have been reduced.

The National Cancer Institute funded the study. The authors reported financial affiliations with Astellas, Celgene, Leadiant Biosciences, Merck, Nabriva Therapeutics, Novartis, Pfizer, Shire, and T2 Biosystems.

SOURCE: Fisher BT et al. JAMA. 2019;322(17):1673-81.

Antifungal prophylaxis with caspofungin led to a lower incidence of invasive fungal disease, compared with fluconazole, in children and young adults with acute myeloid leukemia (AML), according to new study findings.

National Institutes of Health/Wikimedia Commons/Public Domain

The results suggest caspofungin may be an appropriate prophylactic strategy to prevent invasive fungal disease in younger patients with newly diagnosed AML, reported Brian T. Fisher, DO, of the University of Pennsylvania, Philadelphia, and colleagues. The study was published in JAMA.

The randomized, open-label study included 517 children, adolescents, and young adults with de novo, relapsed, or secondary AML. Study patients received treatment in 115 centers throughout United States and Canada. The median age of patients in the study was 9 years (range, 0-26 years); 56% were male and approximately 69% were white.

Study subjects were randomly assigned to receive antifungal prophylaxis with 70 mg/m² (maximum dose 70 mg/day) of intravenous caspofungin on day 1, followed by 50 mg/m² per day (maximum dose 50 mg/day) thereafter, or age-dosed intravenous or oral fluconazole.

Prophylactic therapy was initiated 24-72 hours after the completion of each chemotherapy cycle, and was maintained until the end of the neutropenic period following each cycle.

At 5-month follow-up, the cumulative incidence rate of probable or proven invasive fungal disease was 3.1% (95% confidence interval, 1.3%-7.0%) in the caspofungin arm, compared with 7.2% (95% CI, 4.4%-11.8%) in the fluconazole arm (overall P = .03).

In addition, the 5-month cumulative incidence rate of probable or proven invasive aspergillosis infection was 0.5% (95%CI, 0.1%-3.5%) in patients who received caspofungin, compared with 3.1% (95% CI, 1.4%-6.9%) in patients who received fluconazole (overall P = .046).

“No statistically significant differences in empirical antifungal therapy or 2-year overall survival were observed,” they reported.

With respect to safety, the most frequently reported adverse events were hypokalemia (22 events in the caspofungin arm vs. 13 in the fluconazole arm), respiratory failure (6 events in the caspofungin arm vs. 9 in the fluconazole arm), and elevated alanine transaminase (4 events in the caspofungin arm vs. 8 in the fluconazole arm).

The researchers acknowledged a key limitation of the study was the short duration of follow-up. As a result, the precision of some comparative measures may have been reduced.

The National Cancer Institute funded the study. The authors reported financial affiliations with Astellas, Celgene, Leadiant Biosciences, Merck, Nabriva Therapeutics, Novartis, Pfizer, Shire, and T2 Biosystems.

SOURCE: Fisher BT et al. JAMA. 2019;322(17):1673-81.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

lfranki@mdedge.com

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

lfranki@mdedge.com

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

lfranki@mdedge.com

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

The relationship between the Kingdom of Morocco and the US began just after the US declared its own independence. It is one of the oldest of US partnerships with a foreign country, and since the end of the First Barbary War in 1805 it has remained one of the most stable. The Utah National Guard (UTNG) has an active state partnership program (SPP) with Morocco, which helps maintain that stability and fosters the relationship. The SPP provides the Kingdom of Morocco assistance in the areas of disaster medicine, prehospital medicine, and rural access to health care.

The objective of this review is to highlight the role the SPP plays in ensuring Morocco’s continued stability, enhancing its role as a leader among African nations, aiding its medically vulnerable rural populations to prevent recruitment by terrorist organizations, and maintaining its long-term relationship with the US.

Background

The Kingdom of Morocco resides in a geologically and politically unstable part of the world, yet it has been a stable constitutional monarchy. Like California, Morocco has a long coastline of more than 1,000 miles. It sits along an active earthquake fault line with a disaster response program that is only in its infancy. The Kingdom has a high youth unemployment rate and lacks adequate public education opportunities, which exacerbate feelings of government indifference. Morocco’s medical system is highly centralized, and large parts of the rural population lack access to basic medical care—potentially alienating the population. The Moroccan current disaster plan ORSEC (plan d’ Organization des Secours) was established in 1966 and updated in 2005 but does not provide a comprehensive, unified disaster response. The ORSEC plan is of French derivation and is not a list of actions but a general plan of organization and supply. ¹

When governments fail to provide basic services—health care being just one—those services may be filled by groups seeking to influence the government and population by threatening acts of violence to achieve political, religious, and ideologic gain; for example, the Taliban in Afghanistan, the Muslim brotherhood in Egypt and in the West Bank, and the Islamic State in Iraq and Syria (ISIS) in Syria.^2-5 These groups gain a foothold and legitimacy by providing mosques, youth groups, clinics, hospitals, and schools. ^2-5

Identified Needs

Morocco is at risk of experiencing an earthquake and possible subsequent tsunami. In 1755, Morocco was impacted by the Great Lisbon earthquake and tsunami. Witnesses reported 15-meter waves with 24-meter crests.⁶ Building codes and architecture laws have changed little since the 1960 Agadir earthquake, which killed 12,000 people. The disaster response program—although improved since the 1960s—is still in the early stages of development, and another earthquake and possible subsequent tsunami would result in a disaster that could overwhelm the medical community of Morocco.

Perceived Government Indifference

The Moroccan constitutional monarchy is more stable than are the governments of its North African neighbors. King Mohammed VI presides over the government, and regular elections are held for members of Parliament, which names a prime minister. However, in August 2019, overall unemployment was at 8.5%, and youth unemployment was 22.3%.⁷ A United Nations report in August 2019 stated that literacy rates for Morocco were 71.7%. These data were from a 2015 census, the last year data were collected.⁸ These deficits in employment and education can foster anger toward the Moroccan government for not adequately providing these services and possibly introduce radicalization as a result of the population’s perceived government indifference and lack of economic mobility.

Access to Medical Care

Morocco has a 2-tiered medical system for providing services: urban and rural. In 2018 the Legatum Prosperity Index ranked Morocco 103 of 149 countries in health care. The prosperity index measures health variables, which include but were not limited to basic physical and mental health, health infrastructure, and preventive care.⁹ Outside the metropolitan areas, emergency medical care is nonexistent, primary care is sporadic, and there is little modern technology available.

Despite humanitarian efforts over many years, there is little to no medical care in the rural “medical desert.” A 2017 study from the University of Washington Institute for Health Metrics and Evaluation compared the global burden of disease in similar countries. The study found that Morocco was significantly higher than the mean in the prevalence of ischemic heart disease and Alzheimer disease, lower than the mean in the areas of neonatal disorders, lower respiratory infections, and tuberculosis, and statistically indistinct from the mean in stroke, congenital defects, road injuries, diabetes mellitus, and hypertensive heart disease compared with the disease prevalence of other countries of similar size and economic measures.¹⁰ The study also found a particularly acute disparity in access to health care in rural areas. In 2016, the Oxford Business Group reported staff shortages and disproportionate distribution of resources in the Moroccan health care system.¹¹

Additionally, the lack of trained health care personnel has added to an already overstressed health care system. A chief stressor in a health care system is an insufficient replacement rate. Health employees working for the Moroccan Ministry of Health retire at a rate of 1,500 per year.^10,11 These shortages may serve to further the feelings of frustration and government indifference. This frustration is momentarily decreased by humanitarian efforts that have taken place in the African continent in the past decades, but this band-aid approach to assisting the population that is medically underserved has done little to alleviate the long-term problem of access to care. And feelings of government abandonment can sow the seeds of discontent in the rural population, creating fertile ground for recruitment by terrorist organizations.^2,3

Lack of Health Care and Radicalism

It has been postulated that there is a link between radicalization and lack of medical care. Depression and perceived government indifference are considered contributors to radicalization.^12-16 In 2005, Victoroff suggested that there are certain psychological traits characteristic of “typical" terrorists: these include high affective valence regarding an ideologic issue, a personal stake (perceived oppression, persecution or humiliation, need for identity, glory, or vengeance), low cognitive ability, low tolerance for ambiguity, and a capacity to suppress instinctive and learned moral constraints against harming innocents.¹⁵ In 2009, Lafree and Ackerman suggested that terrorism feeds on the ability of groups to portray governments and their agents as illegitimate.¹⁶ It is possible that part of the illegitimacy campaign of radicalization and terrorist recruitment may be identification of the lack of health care by the government thus magnifying feelings of government abandonment in a vulnerable population.

In 2011, the new Moroccan constitution identified access to basic health care as a right of the Moroccan people.¹⁷ Additionally, in 2013, a government white paper was produced outlining the need to increase access to health care, particularly in rural areas, including a focus on infant and maternal mortality, diabetes mellitus (DM), heart disease, and respiratory problems.^17,18

Proposed Solutions, A Beginning

A health outreach program with a regional health professional training center in a relatively stable country within the African Union (AU) would be a step toward delivering health care to Morocco and interested AU members. Interested nations have been and will continue to be invited to train at the Moroccan center and return to their countries and start training programs. This idea was echoed by the World Bank in a 2015 loan proposal to Morocco, which suggested that addressing disparities in access to health care is a social justice issue, with other benefits such as increased productivity, employment, lower out-of-pocket expenditures, and promotion of good governance.¹⁷

In 2012, Buhi reported that a positive regard for authorities and healthier influences seemed to be a protective factor against radicalization. He also suggested a public health approach to understanding and preventing violent radicalization.¹⁹ The solutions are complex, especially in rural areas and in vulnerable nations common to Africa.

Medical training efforts by the US Department of Defense (DoD), Medical Readiness Training Institute (DMRT), and international health specialists working with the military and civilian entities in neighboring African countries have improved response to regional disasters. However, to address the broader issues, a more permanent, cooperative possible solution may begin with the establishment in Morocco of a regional education center for disaster preparedness and for health care providers (HCPs). This would serve as a training program for disaster first responders. Graduates of the program would receive additional training to become HCPs similar to physician assistant (PA) and nurse practitioner (NP) programs in the US. Morocco is uniquely positioned to accomplish this due to its location, political stability, and ties with other African nations.

The goal of the Moroccan regional education center (within the King Mohammed V Hospital) is to bring together global health experts and increase the intellectual infrastructure of not only Morocco, but also offer this training program to interested countries within the AU. Advancement of the regional education center will require legislative changes to expand prescriptive privileges and scope of practice within each country. The medical element of the SPP as presently constituted without the regional education center will continue its humanitarian goals, but the proposed creation of the regional education center will educate participants to serve the rural communities within each participating country. Eventually the entire educational program will be the responsibility of the Moroccan military and the AU participants. This will require reprioritizing resources from the provision of humanitarian health care services to an HCP education approach.

Disaster Response

Deficits in disaster response capabilities have been identified by members of the Moroccan military with the assistance of the UTNG. The most glaring deficit identified was the disparity in training between military and civilian first responders. Thus, a training program was initiated by the Moroccan military and the UTNG that combined internationally recognized, durable, robust emergency training programs. These programs consisted of, but were not limited to, parts or entire programs of the following: basic disaster life support, advanced disaster life support, disaster casualty care, and advanced trauma life support. The goal of this training was to improve communication, reduce mortality, and create strike teams, which can quickly provide health care independent of a hospital during a disaster.

Patients can overwhelm hospitals in a disaster when need exceeds resources. In 1996, Mallonee reported that at least 67% of the patients who sought care at a hospital during the Oklahoma City bombing disaster did not need advanced medical treatment.²⁰ Such patients could be seen at an identified casualty collection point by a strike team and treated and released rather than traveling to the hospital and using staff and resources that could be used more judiciously for the more seriously injured.²¹ These teams consist of trained first responders with an experienced HCP (physician, PA, NP) and a nurse and are trained to operate for up to 72 hours in a predetermined location and serve as a “filter” for the hospital. Their role is to treat and release the less severely injured and refer only the more severely injured to the hospital after basic stabilization, thus preserving precious resources necessary for the more seriously injured.

This disaster response training program was offered to the Moroccan military, ministry of health and ministry of tourism, and quickly turned into an Africa-wide interest. A regional training center was proposed. This was assisted with the cooperation of Weber State University in Ogden Utah, Utah Valley University in Orem, and private interests in a public/private/military state partnership. Program supplies and didactic instruction were and will be provided by the UTNG and supplemented through the DoD Africa command. Instruction will be a cooperative effort agreed on between the UTNG and the Moroccan military medical specialists within their specific area of expertise.

Underserved Communities

Finally, from this pool of interested strike team members, a health care provider school will be formed to educate, certify, and service the needs of the underserved communities in Morocco and interested AU countries. This program will be similar to the PA and NP programs in the US and will be geared to those graduates from the previous programs with intense classroom instruction for one year followed by a year of one-on-one preceptorship with an experienced physician. The goal of the program is to prepare individuals with patient care experience to fulfill a bigger role in health care in an underserved (usually austere, rural) area that currently has minimal health care presence. This fills a need identified by the World Bank in 2015 that the Moroccan government needs to respond to the demand for improved access to and quality of health care services—particularly to the rural poor.¹⁷

The Moroccan military has a presence in many medically underserved areas. The logical fit for the HCP program will be drawn from a pool of active-duty military individuals who express an interest and qualify through attendance in all phases of the training.

Conclusion

This program of disaster medical education, strike teams, and HCPs is currently training more than 200 students a year throughout Morocco. The proposed direction of this cooperative program to produce HCPs in rural areas will increase access to health care for the Moroccan people who are now underserved. Morocco, as a health care training hub in Africa, will increase access to health care for interested African countries. The goal politically will be to reduce feelings of government indifference in vulnerable populations and reduce recruitment into radical ideologies.

The relationship between the Kingdom of Morocco and the US began just after the US declared its own independence. It is one of the oldest of US partnerships with a foreign country, and since the end of the First Barbary War in 1805 it has remained one of the most stable. The Utah National Guard (UTNG) has an active state partnership program (SPP) with Morocco, which helps maintain that stability and fosters the relationship. The SPP provides the Kingdom of Morocco assistance in the areas of disaster medicine, prehospital medicine, and rural access to health care.

The objective of this review is to highlight the role the SPP plays in ensuring Morocco’s continued stability, enhancing its role as a leader among African nations, aiding its medically vulnerable rural populations to prevent recruitment by terrorist organizations, and maintaining its long-term relationship with the US.

Background

The Kingdom of Morocco resides in a geologically and politically unstable part of the world, yet it has been a stable constitutional monarchy. Like California, Morocco has a long coastline of more than 1,000 miles. It sits along an active earthquake fault line with a disaster response program that is only in its infancy. The Kingdom has a high youth unemployment rate and lacks adequate public education opportunities, which exacerbate feelings of government indifference. Morocco’s medical system is highly centralized, and large parts of the rural population lack access to basic medical care—potentially alienating the population. The Moroccan current disaster plan ORSEC (plan d’ Organization des Secours) was established in 1966 and updated in 2005 but does not provide a comprehensive, unified disaster response. The ORSEC plan is of French derivation and is not a list of actions but a general plan of organization and supply. ¹

When governments fail to provide basic services—health care being just one—those services may be filled by groups seeking to influence the government and population by threatening acts of violence to achieve political, religious, and ideologic gain; for example, the Taliban in Afghanistan, the Muslim brotherhood in Egypt and in the West Bank, and the Islamic State in Iraq and Syria (ISIS) in Syria.^2-5 These groups gain a foothold and legitimacy by providing mosques, youth groups, clinics, hospitals, and schools. ^2-5

Identified Needs

Morocco is at risk of experiencing an earthquake and possible subsequent tsunami. In 1755, Morocco was impacted by the Great Lisbon earthquake and tsunami. Witnesses reported 15-meter waves with 24-meter crests.⁶ Building codes and architecture laws have changed little since the 1960 Agadir earthquake, which killed 12,000 people. The disaster response program—although improved since the 1960s—is still in the early stages of development, and another earthquake and possible subsequent tsunami would result in a disaster that could overwhelm the medical community of Morocco.

Perceived Government Indifference

The Moroccan constitutional monarchy is more stable than are the governments of its North African neighbors. King Mohammed VI presides over the government, and regular elections are held for members of Parliament, which names a prime minister. However, in August 2019, overall unemployment was at 8.5%, and youth unemployment was 22.3%.⁷ A United Nations report in August 2019 stated that literacy rates for Morocco were 71.7%. These data were from a 2015 census, the last year data were collected.⁸ These deficits in employment and education can foster anger toward the Moroccan government for not adequately providing these services and possibly introduce radicalization as a result of the population’s perceived government indifference and lack of economic mobility.

Access to Medical Care

Morocco has a 2-tiered medical system for providing services: urban and rural. In 2018 the Legatum Prosperity Index ranked Morocco 103 of 149 countries in health care. The prosperity index measures health variables, which include but were not limited to basic physical and mental health, health infrastructure, and preventive care.⁹ Outside the metropolitan areas, emergency medical care is nonexistent, primary care is sporadic, and there is little modern technology available.

Despite humanitarian efforts over many years, there is little to no medical care in the rural “medical desert.” A 2017 study from the University of Washington Institute for Health Metrics and Evaluation compared the global burden of disease in similar countries. The study found that Morocco was significantly higher than the mean in the prevalence of ischemic heart disease and Alzheimer disease, lower than the mean in the areas of neonatal disorders, lower respiratory infections, and tuberculosis, and statistically indistinct from the mean in stroke, congenital defects, road injuries, diabetes mellitus, and hypertensive heart disease compared with the disease prevalence of other countries of similar size and economic measures.¹⁰ The study also found a particularly acute disparity in access to health care in rural areas. In 2016, the Oxford Business Group reported staff shortages and disproportionate distribution of resources in the Moroccan health care system.¹¹

Additionally, the lack of trained health care personnel has added to an already overstressed health care system. A chief stressor in a health care system is an insufficient replacement rate. Health employees working for the Moroccan Ministry of Health retire at a rate of 1,500 per year.^10,11 These shortages may serve to further the feelings of frustration and government indifference. This frustration is momentarily decreased by humanitarian efforts that have taken place in the African continent in the past decades, but this band-aid approach to assisting the population that is medically underserved has done little to alleviate the long-term problem of access to care. And feelings of government abandonment can sow the seeds of discontent in the rural population, creating fertile ground for recruitment by terrorist organizations.^2,3

Lack of Health Care and Radicalism

It has been postulated that there is a link between radicalization and lack of medical care. Depression and perceived government indifference are considered contributors to radicalization.^12-16 In 2005, Victoroff suggested that there are certain psychological traits characteristic of “typical" terrorists: these include high affective valence regarding an ideologic issue, a personal stake (perceived oppression, persecution or humiliation, need for identity, glory, or vengeance), low cognitive ability, low tolerance for ambiguity, and a capacity to suppress instinctive and learned moral constraints against harming innocents.¹⁵ In 2009, Lafree and Ackerman suggested that terrorism feeds on the ability of groups to portray governments and their agents as illegitimate.¹⁶ It is possible that part of the illegitimacy campaign of radicalization and terrorist recruitment may be identification of the lack of health care by the government thus magnifying feelings of government abandonment in a vulnerable population.

In 2011, the new Moroccan constitution identified access to basic health care as a right of the Moroccan people.¹⁷ Additionally, in 2013, a government white paper was produced outlining the need to increase access to health care, particularly in rural areas, including a focus on infant and maternal mortality, diabetes mellitus (DM), heart disease, and respiratory problems.^17,18

Proposed Solutions, A Beginning

A health outreach program with a regional health professional training center in a relatively stable country within the African Union (AU) would be a step toward delivering health care to Morocco and interested AU members. Interested nations have been and will continue to be invited to train at the Moroccan center and return to their countries and start training programs. This idea was echoed by the World Bank in a 2015 loan proposal to Morocco, which suggested that addressing disparities in access to health care is a social justice issue, with other benefits such as increased productivity, employment, lower out-of-pocket expenditures, and promotion of good governance.¹⁷

In 2012, Buhi reported that a positive regard for authorities and healthier influences seemed to be a protective factor against radicalization. He also suggested a public health approach to understanding and preventing violent radicalization.¹⁹ The solutions are complex, especially in rural areas and in vulnerable nations common to Africa.

Medical training efforts by the US Department of Defense (DoD), Medical Readiness Training Institute (DMRT), and international health specialists working with the military and civilian entities in neighboring African countries have improved response to regional disasters. However, to address the broader issues, a more permanent, cooperative possible solution may begin with the establishment in Morocco of a regional education center for disaster preparedness and for health care providers (HCPs). This would serve as a training program for disaster first responders. Graduates of the program would receive additional training to become HCPs similar to physician assistant (PA) and nurse practitioner (NP) programs in the US. Morocco is uniquely positioned to accomplish this due to its location, political stability, and ties with other African nations.

The goal of the Moroccan regional education center (within the King Mohammed V Hospital) is to bring together global health experts and increase the intellectual infrastructure of not only Morocco, but also offer this training program to interested countries within the AU. Advancement of the regional education center will require legislative changes to expand prescriptive privileges and scope of practice within each country. The medical element of the SPP as presently constituted without the regional education center will continue its humanitarian goals, but the proposed creation of the regional education center will educate participants to serve the rural communities within each participating country. Eventually the entire educational program will be the responsibility of the Moroccan military and the AU participants. This will require reprioritizing resources from the provision of humanitarian health care services to an HCP education approach.

Disaster Response

Deficits in disaster response capabilities have been identified by members of the Moroccan military with the assistance of the UTNG. The most glaring deficit identified was the disparity in training between military and civilian first responders. Thus, a training program was initiated by the Moroccan military and the UTNG that combined internationally recognized, durable, robust emergency training programs. These programs consisted of, but were not limited to, parts or entire programs of the following: basic disaster life support, advanced disaster life support, disaster casualty care, and advanced trauma life support. The goal of this training was to improve communication, reduce mortality, and create strike teams, which can quickly provide health care independent of a hospital during a disaster.

Patients can overwhelm hospitals in a disaster when need exceeds resources. In 1996, Mallonee reported that at least 67% of the patients who sought care at a hospital during the Oklahoma City bombing disaster did not need advanced medical treatment.²⁰ Such patients could be seen at an identified casualty collection point by a strike team and treated and released rather than traveling to the hospital and using staff and resources that could be used more judiciously for the more seriously injured.²¹ These teams consist of trained first responders with an experienced HCP (physician, PA, NP) and a nurse and are trained to operate for up to 72 hours in a predetermined location and serve as a “filter” for the hospital. Their role is to treat and release the less severely injured and refer only the more severely injured to the hospital after basic stabilization, thus preserving precious resources necessary for the more seriously injured.

This disaster response training program was offered to the Moroccan military, ministry of health and ministry of tourism, and quickly turned into an Africa-wide interest. A regional training center was proposed. This was assisted with the cooperation of Weber State University in Ogden Utah, Utah Valley University in Orem, and private interests in a public/private/military state partnership. Program supplies and didactic instruction were and will be provided by the UTNG and supplemented through the DoD Africa command. Instruction will be a cooperative effort agreed on between the UTNG and the Moroccan military medical specialists within their specific area of expertise.

Underserved Communities

Finally, from this pool of interested strike team members, a health care provider school will be formed to educate, certify, and service the needs of the underserved communities in Morocco and interested AU countries. This program will be similar to the PA and NP programs in the US and will be geared to those graduates from the previous programs with intense classroom instruction for one year followed by a year of one-on-one preceptorship with an experienced physician. The goal of the program is to prepare individuals with patient care experience to fulfill a bigger role in health care in an underserved (usually austere, rural) area that currently has minimal health care presence. This fills a need identified by the World Bank in 2015 that the Moroccan government needs to respond to the demand for improved access to and quality of health care services—particularly to the rural poor.¹⁷

The Moroccan military has a presence in many medically underserved areas. The logical fit for the HCP program will be drawn from a pool of active-duty military individuals who express an interest and qualify through attendance in all phases of the training.

Conclusion

This program of disaster medical education, strike teams, and HCPs is currently training more than 200 students a year throughout Morocco. The proposed direction of this cooperative program to produce HCPs in rural areas will increase access to health care for the Moroccan people who are now underserved. Morocco, as a health care training hub in Africa, will increase access to health care for interested African countries. The goal politically will be to reduce feelings of government indifference in vulnerable populations and reduce recruitment into radical ideologies.

The relationship between the Kingdom of Morocco and the US began just after the US declared its own independence. It is one of the oldest of US partnerships with a foreign country, and since the end of the First Barbary War in 1805 it has remained one of the most stable. The Utah National Guard (UTNG) has an active state partnership program (SPP) with Morocco, which helps maintain that stability and fosters the relationship. The SPP provides the Kingdom of Morocco assistance in the areas of disaster medicine, prehospital medicine, and rural access to health care.

The objective of this review is to highlight the role the SPP plays in ensuring Morocco’s continued stability, enhancing its role as a leader among African nations, aiding its medically vulnerable rural populations to prevent recruitment by terrorist organizations, and maintaining its long-term relationship with the US.

Background

The Kingdom of Morocco resides in a geologically and politically unstable part of the world, yet it has been a stable constitutional monarchy. Like California, Morocco has a long coastline of more than 1,000 miles. It sits along an active earthquake fault line with a disaster response program that is only in its infancy. The Kingdom has a high youth unemployment rate and lacks adequate public education opportunities, which exacerbate feelings of government indifference. Morocco’s medical system is highly centralized, and large parts of the rural population lack access to basic medical care—potentially alienating the population. The Moroccan current disaster plan ORSEC (plan d’ Organization des Secours) was established in 1966 and updated in 2005 but does not provide a comprehensive, unified disaster response. The ORSEC plan is of French derivation and is not a list of actions but a general plan of organization and supply. ¹

When governments fail to provide basic services—health care being just one—those services may be filled by groups seeking to influence the government and population by threatening acts of violence to achieve political, religious, and ideologic gain; for example, the Taliban in Afghanistan, the Muslim brotherhood in Egypt and in the West Bank, and the Islamic State in Iraq and Syria (ISIS) in Syria.^2-5 These groups gain a foothold and legitimacy by providing mosques, youth groups, clinics, hospitals, and schools. ^2-5

Identified Needs

Morocco is at risk of experiencing an earthquake and possible subsequent tsunami. In 1755, Morocco was impacted by the Great Lisbon earthquake and tsunami. Witnesses reported 15-meter waves with 24-meter crests.⁶ Building codes and architecture laws have changed little since the 1960 Agadir earthquake, which killed 12,000 people. The disaster response program—although improved since the 1960s—is still in the early stages of development, and another earthquake and possible subsequent tsunami would result in a disaster that could overwhelm the medical community of Morocco.

Perceived Government Indifference

The Moroccan constitutional monarchy is more stable than are the governments of its North African neighbors. King Mohammed VI presides over the government, and regular elections are held for members of Parliament, which names a prime minister. However, in August 2019, overall unemployment was at 8.5%, and youth unemployment was 22.3%.⁷ A United Nations report in August 2019 stated that literacy rates for Morocco were 71.7%. These data were from a 2015 census, the last year data were collected.⁸ These deficits in employment and education can foster anger toward the Moroccan government for not adequately providing these services and possibly introduce radicalization as a result of the population’s perceived government indifference and lack of economic mobility.

Access to Medical Care

Morocco has a 2-tiered medical system for providing services: urban and rural. In 2018 the Legatum Prosperity Index ranked Morocco 103 of 149 countries in health care. The prosperity index measures health variables, which include but were not limited to basic physical and mental health, health infrastructure, and preventive care.⁹ Outside the metropolitan areas, emergency medical care is nonexistent, primary care is sporadic, and there is little modern technology available.

Despite humanitarian efforts over many years, there is little to no medical care in the rural “medical desert.” A 2017 study from the University of Washington Institute for Health Metrics and Evaluation compared the global burden of disease in similar countries. The study found that Morocco was significantly higher than the mean in the prevalence of ischemic heart disease and Alzheimer disease, lower than the mean in the areas of neonatal disorders, lower respiratory infections, and tuberculosis, and statistically indistinct from the mean in stroke, congenital defects, road injuries, diabetes mellitus, and hypertensive heart disease compared with the disease prevalence of other countries of similar size and economic measures.¹⁰ The study also found a particularly acute disparity in access to health care in rural areas. In 2016, the Oxford Business Group reported staff shortages and disproportionate distribution of resources in the Moroccan health care system.¹¹

Additionally, the lack of trained health care personnel has added to an already overstressed health care system. A chief stressor in a health care system is an insufficient replacement rate. Health employees working for the Moroccan Ministry of Health retire at a rate of 1,500 per year.^10,11 These shortages may serve to further the feelings of frustration and government indifference. This frustration is momentarily decreased by humanitarian efforts that have taken place in the African continent in the past decades, but this band-aid approach to assisting the population that is medically underserved has done little to alleviate the long-term problem of access to care. And feelings of government abandonment can sow the seeds of discontent in the rural population, creating fertile ground for recruitment by terrorist organizations.^2,3

Lack of Health Care and Radicalism

It has been postulated that there is a link between radicalization and lack of medical care. Depression and perceived government indifference are considered contributors to radicalization.^12-16 In 2005, Victoroff suggested that there are certain psychological traits characteristic of “typical" terrorists: these include high affective valence regarding an ideologic issue, a personal stake (perceived oppression, persecution or humiliation, need for identity, glory, or vengeance), low cognitive ability, low tolerance for ambiguity, and a capacity to suppress instinctive and learned moral constraints against harming innocents.¹⁵ In 2009, Lafree and Ackerman suggested that terrorism feeds on the ability of groups to portray governments and their agents as illegitimate.¹⁶ It is possible that part of the illegitimacy campaign of radicalization and terrorist recruitment may be identification of the lack of health care by the government thus magnifying feelings of government abandonment in a vulnerable population.

In 2011, the new Moroccan constitution identified access to basic health care as a right of the Moroccan people.¹⁷ Additionally, in 2013, a government white paper was produced outlining the need to increase access to health care, particularly in rural areas, including a focus on infant and maternal mortality, diabetes mellitus (DM), heart disease, and respiratory problems.^17,18

Proposed Solutions, A Beginning

A health outreach program with a regional health professional training center in a relatively stable country within the African Union (AU) would be a step toward delivering health care to Morocco and interested AU members. Interested nations have been and will continue to be invited to train at the Moroccan center and return to their countries and start training programs. This idea was echoed by the World Bank in a 2015 loan proposal to Morocco, which suggested that addressing disparities in access to health care is a social justice issue, with other benefits such as increased productivity, employment, lower out-of-pocket expenditures, and promotion of good governance.¹⁷

In 2012, Buhi reported that a positive regard for authorities and healthier influences seemed to be a protective factor against radicalization. He also suggested a public health approach to understanding and preventing violent radicalization.¹⁹ The solutions are complex, especially in rural areas and in vulnerable nations common to Africa.

Medical training efforts by the US Department of Defense (DoD), Medical Readiness Training Institute (DMRT), and international health specialists working with the military and civilian entities in neighboring African countries have improved response to regional disasters. However, to address the broader issues, a more permanent, cooperative possible solution may begin with the establishment in Morocco of a regional education center for disaster preparedness and for health care providers (HCPs). This would serve as a training program for disaster first responders. Graduates of the program would receive additional training to become HCPs similar to physician assistant (PA) and nurse practitioner (NP) programs in the US. Morocco is uniquely positioned to accomplish this due to its location, political stability, and ties with other African nations.

The goal of the Moroccan regional education center (within the King Mohammed V Hospital) is to bring together global health experts and increase the intellectual infrastructure of not only Morocco, but also offer this training program to interested countries within the AU. Advancement of the regional education center will require legislative changes to expand prescriptive privileges and scope of practice within each country. The medical element of the SPP as presently constituted without the regional education center will continue its humanitarian goals, but the proposed creation of the regional education center will educate participants to serve the rural communities within each participating country. Eventually the entire educational program will be the responsibility of the Moroccan military and the AU participants. This will require reprioritizing resources from the provision of humanitarian health care services to an HCP education approach.

Disaster Response

Deficits in disaster response capabilities have been identified by members of the Moroccan military with the assistance of the UTNG. The most glaring deficit identified was the disparity in training between military and civilian first responders. Thus, a training program was initiated by the Moroccan military and the UTNG that combined internationally recognized, durable, robust emergency training programs. These programs consisted of, but were not limited to, parts or entire programs of the following: basic disaster life support, advanced disaster life support, disaster casualty care, and advanced trauma life support. The goal of this training was to improve communication, reduce mortality, and create strike teams, which can quickly provide health care independent of a hospital during a disaster.

Patients can overwhelm hospitals in a disaster when need exceeds resources. In 1996, Mallonee reported that at least 67% of the patients who sought care at a hospital during the Oklahoma City bombing disaster did not need advanced medical treatment.²⁰ Such patients could be seen at an identified casualty collection point by a strike team and treated and released rather than traveling to the hospital and using staff and resources that could be used more judiciously for the more seriously injured.²¹ These teams consist of trained first responders with an experienced HCP (physician, PA, NP) and a nurse and are trained to operate for up to 72 hours in a predetermined location and serve as a “filter” for the hospital. Their role is to treat and release the less severely injured and refer only the more severely injured to the hospital after basic stabilization, thus preserving precious resources necessary for the more seriously injured.

This disaster response training program was offered to the Moroccan military, ministry of health and ministry of tourism, and quickly turned into an Africa-wide interest. A regional training center was proposed. This was assisted with the cooperation of Weber State University in Ogden Utah, Utah Valley University in Orem, and private interests in a public/private/military state partnership. Program supplies and didactic instruction were and will be provided by the UTNG and supplemented through the DoD Africa command. Instruction will be a cooperative effort agreed on between the UTNG and the Moroccan military medical specialists within their specific area of expertise.

Underserved Communities

Finally, from this pool of interested strike team members, a health care provider school will be formed to educate, certify, and service the needs of the underserved communities in Morocco and interested AU countries. This program will be similar to the PA and NP programs in the US and will be geared to those graduates from the previous programs with intense classroom instruction for one year followed by a year of one-on-one preceptorship with an experienced physician. The goal of the program is to prepare individuals with patient care experience to fulfill a bigger role in health care in an underserved (usually austere, rural) area that currently has minimal health care presence. This fills a need identified by the World Bank in 2015 that the Moroccan government needs to respond to the demand for improved access to and quality of health care services—particularly to the rural poor.¹⁷

The Moroccan military has a presence in many medically underserved areas. The logical fit for the HCP program will be drawn from a pool of active-duty military individuals who express an interest and qualify through attendance in all phases of the training.

Conclusion

This program of disaster medical education, strike teams, and HCPs is currently training more than 200 students a year throughout Morocco. The proposed direction of this cooperative program to produce HCPs in rural areas will increase access to health care for the Moroccan people who are now underserved. Morocco, as a health care training hub in Africa, will increase access to health care for interested African countries. The goal politically will be to reduce feelings of government indifference in vulnerable populations and reduce recruitment into radical ideologies.

NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.

Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.

SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.

NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.

Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.

SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.

NEW ORLEANS – In patients with interstitial lung diseases at risk of pulmonary hypertension, inhaled nitric oxide produced meaningful improvements in activity that have been maintained over the long term, an investigator reported here.

Inhaled nitric oxide, which improved moderate to vigorous physical activity by 34% versus placebo in an 8-week controlled trial, has demonstrated long-term maintenance of activity parameters in open-label extension data, presented at the annual meeting of the American College of Chest Physicians.

SOURCE: Nathan SD et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.308.

Do health effects of menopausal estrogen therapy differ between women with bilateral oophorectomy versus those with conserved ovaries? To answer this question a group of investigators performed a subanalysis of the Women’s Health Initiative (WHI) Estrogen-Alone Trial,¹ which included 40 clinical centers across the United States. They examined estrogen therapy outcomes by bilateral salpingo-oophorectomy (BSO) status, with additional stratification by 10-year age groups in 9,939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. In the WHI trial, women were randomly assigned to conjugated equine estrogens (CEE) 0.625 mg/d or placebo for a median of 7.2 years. Investigators assessed the incidence of coronary heart disease and invasive breast cancer (the trial’s 2 primary end points), all-cause mortality, and a “global index”—these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture—during the intervention phase and 18-year cumulative follow-up.

OBG Management caught up with lead author JoAnn E. Manson, MD, DrPH, NCMP, to discuss the study’s results.
 

OBG Management: How many women undergo BSO with their hysterectomy?

Dr. JoAnn E. Manson, MD, DrPH, NCMP: Of the 425,000 women who undergo hysterectomy in the United States for benign reasons each year,^2,3 about 40% of them undergo BSO—so between 150,000 and 200,000 women per year undergo BSO with their hysterectomy.^4,5
 

OBG Management: Although BSO is performed with hysterectomy to minimize patients’ future ovarian cancer risk, does BSO have health risks of its own, and how has estrogen been shown to affect these risks?

Dr. Manson: First, yes, BSO has been associated with health risks, especially when it is performed at a young age, such as before age 45. It has been linked to an increased risk of heart disease, osteoporosis, cognitive decline, and all-cause mortality. According to observational studies, estrogen therapy appears to offset many of these risks, particularly those related to heart disease and osteoporosis (the evidence is less clear on cognitive deficits).⁵
 

OBG Management: What did you find in your trial when you randomly assigned women in the age groups of 50 to 79 who underwent hysterectomy with and without BSO to estrogen therapy or placebo?

Dr. Manson: The WHI is the first study to be conducted in a randomized trial setting to analyze the health risks and benefits of estrogen therapy according to whether or not women had their ovaries removed. What we found was that the woman’s age had a strong influence on the effects of estrogen therapy among women who had BSO but only a negligible effect among women who had conserved ovaries. Overall, across the full age range, the effects of estrogen therapy did not differ substantially between women who had a BSO and those who had their ovaries conserved.

However, there were major differences by age group among the women who had BSO. A significant 32% reduction in all-cause mortality emerged during the 18-year follow-up period among the younger women (below age 60) who had BSO when they received estrogen therapy as compared with placebo. By contrast, the women who had conserved ovaries did not have this significant reduction in all-cause mortality, or in most of the other outcomes on estrogen compared with placebo. Overall, the effects of estrogen therapy tended to be relatively neutral in the women with conserved ovaries.

Now, the reduction in all-cause mortality with estrogen therapy was particularly pronounced among women who had BSO before age 45. They had a 40% statistically significant reduction in all-cause mortality with estrogen therapy compared with placebo. Also, among the women with BSO, there was a strong association between the timing of estrogen initiation and the magnitude of reduction in mortality. Women who started the estrogen therapy within 10 years of having the BSO had a 34% significant reduction in all-cause mortality, and those who started estrogen more than 20 years after having their ovaries removed had no reduction in mortality.
 

Continue to: OBG Management: Do your data give support to the timing hypothesis?

OBG Management: Do your data give support to the timing hypothesis?

Dr. Manson: Yes, our findings do support a timing hypothesis that was particularly pronounced for women who underwent BSO. It was the women who had early surgical menopause (before age 45) and those who started the estrogen therapy within 10 years of having their ovaries removed who had the greatest reduction in all-cause mortality and the most favorable benefit-risk profile from hormone therapy. So, the results do lend support to the timing hypothesis.

By contrast, women who had BSO at hysterectomy and began hormone therapy at age 70 or older had net adverse effects from hormone therapy. They posted a 40% increase in the global index—which is a summary measure of adverse effects on cardiovascular disease, cancer, and other major health outcomes. So, the women with BSO who were randomized in the trial at age 70 and older, had unfavorable results from estrogen therapy and an increase in the global index, in contrast to the women who were below age 60 or within 10 years of menopause.
 

OBG Management: Given your study findings, in which women would you recommend estrogen therapy? And are there groups of women in which you would advise avoiding estrogen therapy?

Dr. Manson: Current guidelines^6,7 recommend estrogen therapy for women who have early menopause, particularly an early surgical menopause and BSO prior to the average age at natural menopause. Unless the woman has contraindications to estrogen therapy, the recommendations are to treat with estrogen until the average age of menopause—until about age 50 to 51.

Our study findings provide reassurance that, if a woman continues to have indications for estrogen (vasomotor symptoms, or other indications for estrogen therapy), there is relative safety of continuing estrogen-alone therapy through her 50s, until age 60. For example, a woman who, after the average age of menopause continues to have vasomotor symptoms, or if she has bone health problems, our study would suggest that estrogen therapy would continue to have a favorable benefit-risk profile until at least the age of 60. Decisions would have to be individualized, especially after age 60, with shared decision-making particularly important for those decisions. (Some women, depending on their risk profile, may continue to be candidates for estrogen therapy past age 60.)

So, this study provides reassurance regarding use of estrogen therapy for women in their 50s if they have had BSO. Actually, the women who had conserved ovaries also had relative safety with estrogen therapy until age 60. They just didn’t show the significant benefits for all-cause mortality. Overall, their pattern of health-related benefits and risks was neutral. Thus, if vasomotor symptom management, quality of life benefits, or bone health effects are sought, taking hormone therapy is a quite reasonable choice for these women.

By contrast, women who have had a BSO and are age 70 or older should really avoid initiating estrogen therapy because it would follow a prolonged period of estrogen deficiency, or very low estrogen levels, and these women appeared to have a net adverse effect from initiating hormone therapy (with increases in the global index found).

Continue to: OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

Dr. Manson: We found minimal if any effect in our analyses. In fact, even the women who did not have prior (pre-randomization) use of estrogen therapy tended to do well on estrogen-alone therapy if they were younger than age 60. This was particularly true for the women who had BSO. Even if they had not used estrogen previously, and they were many years past the BSO, they still did well on estrogen therapy if they were below age 60.

Do health effects of menopausal estrogen therapy differ between women with bilateral oophorectomy versus those with conserved ovaries? To answer this question a group of investigators performed a subanalysis of the Women’s Health Initiative (WHI) Estrogen-Alone Trial,¹ which included 40 clinical centers across the United States. They examined estrogen therapy outcomes by bilateral salpingo-oophorectomy (BSO) status, with additional stratification by 10-year age groups in 9,939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. In the WHI trial, women were randomly assigned to conjugated equine estrogens (CEE) 0.625 mg/d or placebo for a median of 7.2 years. Investigators assessed the incidence of coronary heart disease and invasive breast cancer (the trial’s 2 primary end points), all-cause mortality, and a “global index”—these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture—during the intervention phase and 18-year cumulative follow-up.

OBG Management caught up with lead author JoAnn E. Manson, MD, DrPH, NCMP, to discuss the study’s results.
 

OBG Management: How many women undergo BSO with their hysterectomy?

Dr. JoAnn E. Manson, MD, DrPH, NCMP: Of the 425,000 women who undergo hysterectomy in the United States for benign reasons each year,^2,3 about 40% of them undergo BSO—so between 150,000 and 200,000 women per year undergo BSO with their hysterectomy.^4,5
 

OBG Management: Although BSO is performed with hysterectomy to minimize patients’ future ovarian cancer risk, does BSO have health risks of its own, and how has estrogen been shown to affect these risks?

Dr. Manson: First, yes, BSO has been associated with health risks, especially when it is performed at a young age, such as before age 45. It has been linked to an increased risk of heart disease, osteoporosis, cognitive decline, and all-cause mortality. According to observational studies, estrogen therapy appears to offset many of these risks, particularly those related to heart disease and osteoporosis (the evidence is less clear on cognitive deficits).⁵
 

OBG Management: What did you find in your trial when you randomly assigned women in the age groups of 50 to 79 who underwent hysterectomy with and without BSO to estrogen therapy or placebo?

Dr. Manson: The WHI is the first study to be conducted in a randomized trial setting to analyze the health risks and benefits of estrogen therapy according to whether or not women had their ovaries removed. What we found was that the woman’s age had a strong influence on the effects of estrogen therapy among women who had BSO but only a negligible effect among women who had conserved ovaries. Overall, across the full age range, the effects of estrogen therapy did not differ substantially between women who had a BSO and those who had their ovaries conserved.

However, there were major differences by age group among the women who had BSO. A significant 32% reduction in all-cause mortality emerged during the 18-year follow-up period among the younger women (below age 60) who had BSO when they received estrogen therapy as compared with placebo. By contrast, the women who had conserved ovaries did not have this significant reduction in all-cause mortality, or in most of the other outcomes on estrogen compared with placebo. Overall, the effects of estrogen therapy tended to be relatively neutral in the women with conserved ovaries.

Now, the reduction in all-cause mortality with estrogen therapy was particularly pronounced among women who had BSO before age 45. They had a 40% statistically significant reduction in all-cause mortality with estrogen therapy compared with placebo. Also, among the women with BSO, there was a strong association between the timing of estrogen initiation and the magnitude of reduction in mortality. Women who started the estrogen therapy within 10 years of having the BSO had a 34% significant reduction in all-cause mortality, and those who started estrogen more than 20 years after having their ovaries removed had no reduction in mortality.
 

Continue to: OBG Management: Do your data give support to the timing hypothesis?

OBG Management: Do your data give support to the timing hypothesis?

Dr. Manson: Yes, our findings do support a timing hypothesis that was particularly pronounced for women who underwent BSO. It was the women who had early surgical menopause (before age 45) and those who started the estrogen therapy within 10 years of having their ovaries removed who had the greatest reduction in all-cause mortality and the most favorable benefit-risk profile from hormone therapy. So, the results do lend support to the timing hypothesis.

By contrast, women who had BSO at hysterectomy and began hormone therapy at age 70 or older had net adverse effects from hormone therapy. They posted a 40% increase in the global index—which is a summary measure of adverse effects on cardiovascular disease, cancer, and other major health outcomes. So, the women with BSO who were randomized in the trial at age 70 and older, had unfavorable results from estrogen therapy and an increase in the global index, in contrast to the women who were below age 60 or within 10 years of menopause.
 

OBG Management: Given your study findings, in which women would you recommend estrogen therapy? And are there groups of women in which you would advise avoiding estrogen therapy?

Dr. Manson: Current guidelines^6,7 recommend estrogen therapy for women who have early menopause, particularly an early surgical menopause and BSO prior to the average age at natural menopause. Unless the woman has contraindications to estrogen therapy, the recommendations are to treat with estrogen until the average age of menopause—until about age 50 to 51.

Our study findings provide reassurance that, if a woman continues to have indications for estrogen (vasomotor symptoms, or other indications for estrogen therapy), there is relative safety of continuing estrogen-alone therapy through her 50s, until age 60. For example, a woman who, after the average age of menopause continues to have vasomotor symptoms, or if she has bone health problems, our study would suggest that estrogen therapy would continue to have a favorable benefit-risk profile until at least the age of 60. Decisions would have to be individualized, especially after age 60, with shared decision-making particularly important for those decisions. (Some women, depending on their risk profile, may continue to be candidates for estrogen therapy past age 60.)

So, this study provides reassurance regarding use of estrogen therapy for women in their 50s if they have had BSO. Actually, the women who had conserved ovaries also had relative safety with estrogen therapy until age 60. They just didn’t show the significant benefits for all-cause mortality. Overall, their pattern of health-related benefits and risks was neutral. Thus, if vasomotor symptom management, quality of life benefits, or bone health effects are sought, taking hormone therapy is a quite reasonable choice for these women.

By contrast, women who have had a BSO and are age 70 or older should really avoid initiating estrogen therapy because it would follow a prolonged period of estrogen deficiency, or very low estrogen levels, and these women appeared to have a net adverse effect from initiating hormone therapy (with increases in the global index found).

Continue to: OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

Dr. Manson: We found minimal if any effect in our analyses. In fact, even the women who did not have prior (pre-randomization) use of estrogen therapy tended to do well on estrogen-alone therapy if they were younger than age 60. This was particularly true for the women who had BSO. Even if they had not used estrogen previously, and they were many years past the BSO, they still did well on estrogen therapy if they were below age 60.

Do health effects of menopausal estrogen therapy differ between women with bilateral oophorectomy versus those with conserved ovaries? To answer this question a group of investigators performed a subanalysis of the Women’s Health Initiative (WHI) Estrogen-Alone Trial,¹ which included 40 clinical centers across the United States. They examined estrogen therapy outcomes by bilateral salpingo-oophorectomy (BSO) status, with additional stratification by 10-year age groups in 9,939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. In the WHI trial, women were randomly assigned to conjugated equine estrogens (CEE) 0.625 mg/d or placebo for a median of 7.2 years. Investigators assessed the incidence of coronary heart disease and invasive breast cancer (the trial’s 2 primary end points), all-cause mortality, and a “global index”—these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture—during the intervention phase and 18-year cumulative follow-up.

OBG Management caught up with lead author JoAnn E. Manson, MD, DrPH, NCMP, to discuss the study’s results.
 

OBG Management: How many women undergo BSO with their hysterectomy?

Dr. JoAnn E. Manson, MD, DrPH, NCMP: Of the 425,000 women who undergo hysterectomy in the United States for benign reasons each year,^2,3 about 40% of them undergo BSO—so between 150,000 and 200,000 women per year undergo BSO with their hysterectomy.^4,5
 

OBG Management: Although BSO is performed with hysterectomy to minimize patients’ future ovarian cancer risk, does BSO have health risks of its own, and how has estrogen been shown to affect these risks?

Dr. Manson: First, yes, BSO has been associated with health risks, especially when it is performed at a young age, such as before age 45. It has been linked to an increased risk of heart disease, osteoporosis, cognitive decline, and all-cause mortality. According to observational studies, estrogen therapy appears to offset many of these risks, particularly those related to heart disease and osteoporosis (the evidence is less clear on cognitive deficits).⁵
 

OBG Management: What did you find in your trial when you randomly assigned women in the age groups of 50 to 79 who underwent hysterectomy with and without BSO to estrogen therapy or placebo?

Dr. Manson: The WHI is the first study to be conducted in a randomized trial setting to analyze the health risks and benefits of estrogen therapy according to whether or not women had their ovaries removed. What we found was that the woman’s age had a strong influence on the effects of estrogen therapy among women who had BSO but only a negligible effect among women who had conserved ovaries. Overall, across the full age range, the effects of estrogen therapy did not differ substantially between women who had a BSO and those who had their ovaries conserved.

However, there were major differences by age group among the women who had BSO. A significant 32% reduction in all-cause mortality emerged during the 18-year follow-up period among the younger women (below age 60) who had BSO when they received estrogen therapy as compared with placebo. By contrast, the women who had conserved ovaries did not have this significant reduction in all-cause mortality, or in most of the other outcomes on estrogen compared with placebo. Overall, the effects of estrogen therapy tended to be relatively neutral in the women with conserved ovaries.

Now, the reduction in all-cause mortality with estrogen therapy was particularly pronounced among women who had BSO before age 45. They had a 40% statistically significant reduction in all-cause mortality with estrogen therapy compared with placebo. Also, among the women with BSO, there was a strong association between the timing of estrogen initiation and the magnitude of reduction in mortality. Women who started the estrogen therapy within 10 years of having the BSO had a 34% significant reduction in all-cause mortality, and those who started estrogen more than 20 years after having their ovaries removed had no reduction in mortality.
 

Continue to: OBG Management: Do your data give support to the timing hypothesis?

OBG Management: Do your data give support to the timing hypothesis?

Dr. Manson: Yes, our findings do support a timing hypothesis that was particularly pronounced for women who underwent BSO. It was the women who had early surgical menopause (before age 45) and those who started the estrogen therapy within 10 years of having their ovaries removed who had the greatest reduction in all-cause mortality and the most favorable benefit-risk profile from hormone therapy. So, the results do lend support to the timing hypothesis.

By contrast, women who had BSO at hysterectomy and began hormone therapy at age 70 or older had net adverse effects from hormone therapy. They posted a 40% increase in the global index—which is a summary measure of adverse effects on cardiovascular disease, cancer, and other major health outcomes. So, the women with BSO who were randomized in the trial at age 70 and older, had unfavorable results from estrogen therapy and an increase in the global index, in contrast to the women who were below age 60 or within 10 years of menopause.
 

OBG Management: Given your study findings, in which women would you recommend estrogen therapy? And are there groups of women in which you would advise avoiding estrogen therapy?

Dr. Manson: Current guidelines^6,7 recommend estrogen therapy for women who have early menopause, particularly an early surgical menopause and BSO prior to the average age at natural menopause. Unless the woman has contraindications to estrogen therapy, the recommendations are to treat with estrogen until the average age of menopause—until about age 50 to 51.

Our study findings provide reassurance that, if a woman continues to have indications for estrogen (vasomotor symptoms, or other indications for estrogen therapy), there is relative safety of continuing estrogen-alone therapy through her 50s, until age 60. For example, a woman who, after the average age of menopause continues to have vasomotor symptoms, or if she has bone health problems, our study would suggest that estrogen therapy would continue to have a favorable benefit-risk profile until at least the age of 60. Decisions would have to be individualized, especially after age 60, with shared decision-making particularly important for those decisions. (Some women, depending on their risk profile, may continue to be candidates for estrogen therapy past age 60.)

So, this study provides reassurance regarding use of estrogen therapy for women in their 50s if they have had BSO. Actually, the women who had conserved ovaries also had relative safety with estrogen therapy until age 60. They just didn’t show the significant benefits for all-cause mortality. Overall, their pattern of health-related benefits and risks was neutral. Thus, if vasomotor symptom management, quality of life benefits, or bone health effects are sought, taking hormone therapy is a quite reasonable choice for these women.

By contrast, women who have had a BSO and are age 70 or older should really avoid initiating estrogen therapy because it would follow a prolonged period of estrogen deficiency, or very low estrogen levels, and these women appeared to have a net adverse effect from initiating hormone therapy (with increases in the global index found).

Continue to: OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

Dr. Manson: We found minimal if any effect in our analyses. In fact, even the women who did not have prior (pre-randomization) use of estrogen therapy tended to do well on estrogen-alone therapy if they were younger than age 60. This was particularly true for the women who had BSO. Even if they had not used estrogen previously, and they were many years past the BSO, they still did well on estrogen therapy if they were below age 60.