Less and less of the research presented at a prominent cancer conference is supported by the National Institutes of Health, a development that some of the country’s top scientists see as a worrisome trend.

The number of studies fully funded by the NIH at the annual meeting of the American Society of Clinical Oncology (ASCO) – the world’s largest gathering of cancer researchers – has fallen 75% in the past decade, from 575 papers in 2008 to 144 this year, according to the society, which meets June 2-6 in Chicago.

American researchers typically dominate the meeting’s press conferences – designed to feature the most important and newsworthy research. This year, there are 14 studies led by international scientists versus 12 led by U.S.-based research teams. That’s a big shift from just 5 years ago, when 15 studies in the “press program” were led by Americans versus 9 by international researchers.

Several of the studies on this weekend’s press program come from Europe and Canada, along with two from China.

President Donald Trump has proposed cutting the NIH budget for 2018 from $31.8 billion to $26 billion, a decline that many worry would jeopardize the fight against cancer and other diseases. Those cuts include $1 billion less for the National Cancer Institute.

On its website, the NCI notes that its purchasing power already has declined by 25% since 2003, because its budget – while growing – hasn’t kept up with inflation. Congress gave the NCI nearly $5.4 billion in fiscal year 2017, an increase of $174.6 million over last year. The NCI also received $300 million for the Beau Biden Cancer Moonshot through the 21st Century Cures Act in December 2016.

“America may be losing its edge in medical research,” said Otis Brawley, MD, chief medical officer at the American Cancer Society. The brightest young scientists are having trouble finding funding for their research, leading them to look for jobs not at universities but at drug companies “or even Wall Street,” he said. “I fear we are losing a generation of young, talented biomedical scientists.”

Some see America’s leading role in science as a point of national pride.

“Do we want the U.S. to remain at the center of biomedical innovation, or do we want to cede that to China or other countries?” said Dr. Stephan Grupp, director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia. “If you don’t push to stay in front, you don’t stay in front.”

But more than pride is at stake.

Public funding is critical, because it allows researchers to answer questions that don’t interest drug companies, said Richard Schilsky, senior vice president and chief medical officer at ASCO.

While drug companies fund studies that help them get their medications approved, they tend not to pay for studies that focus on cancer prevention, screening, or quality of life, Mr. Schilsky said. The NIH also funds head-to-head comparisons of cancer drugs, which allow patients and doctors to select the most effective treatments.

“If the NIH-funded studies continue to decline, we simply won’t get the answers that patients are looking for,” he said.

While government research often addresses areas of greatest need, “industry research is geared toward marketable products,” Dr. Brawley said.

To help make up the deficit, the American Cancer Society will double its research budget to $240 million by 2021, he added.

But Dr. Grupp notes that charities and the drug industry are often reluctant to cover the indirect costs of research, such as labs. Without steady, predictable support from government grants, Dr. Grupp said he wouldn’t “have a building to do my research in or a way to keep the lights on.”


 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Less and less of the research presented at a prominent cancer conference is supported by the National Institutes of Health, a development that some of the country’s top scientists see as a worrisome trend.

The number of studies fully funded by the NIH at the annual meeting of the American Society of Clinical Oncology (ASCO) – the world’s largest gathering of cancer researchers – has fallen 75% in the past decade, from 575 papers in 2008 to 144 this year, according to the society, which meets June 2-6 in Chicago.

American researchers typically dominate the meeting’s press conferences – designed to feature the most important and newsworthy research. This year, there are 14 studies led by international scientists versus 12 led by U.S.-based research teams. That’s a big shift from just 5 years ago, when 15 studies in the “press program” were led by Americans versus 9 by international researchers.

Several of the studies on this weekend’s press program come from Europe and Canada, along with two from China.

President Donald Trump has proposed cutting the NIH budget for 2018 from $31.8 billion to $26 billion, a decline that many worry would jeopardize the fight against cancer and other diseases. Those cuts include $1 billion less for the National Cancer Institute.

On its website, the NCI notes that its purchasing power already has declined by 25% since 2003, because its budget – while growing – hasn’t kept up with inflation. Congress gave the NCI nearly $5.4 billion in fiscal year 2017, an increase of $174.6 million over last year. The NCI also received $300 million for the Beau Biden Cancer Moonshot through the 21st Century Cures Act in December 2016.

“America may be losing its edge in medical research,” said Otis Brawley, MD, chief medical officer at the American Cancer Society. The brightest young scientists are having trouble finding funding for their research, leading them to look for jobs not at universities but at drug companies “or even Wall Street,” he said. “I fear we are losing a generation of young, talented biomedical scientists.”

Some see America’s leading role in science as a point of national pride.

“Do we want the U.S. to remain at the center of biomedical innovation, or do we want to cede that to China or other countries?” said Dr. Stephan Grupp, director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia. “If you don’t push to stay in front, you don’t stay in front.”

But more than pride is at stake.

Public funding is critical, because it allows researchers to answer questions that don’t interest drug companies, said Richard Schilsky, senior vice president and chief medical officer at ASCO.

While drug companies fund studies that help them get their medications approved, they tend not to pay for studies that focus on cancer prevention, screening, or quality of life, Mr. Schilsky said. The NIH also funds head-to-head comparisons of cancer drugs, which allow patients and doctors to select the most effective treatments.

“If the NIH-funded studies continue to decline, we simply won’t get the answers that patients are looking for,” he said.

While government research often addresses areas of greatest need, “industry research is geared toward marketable products,” Dr. Brawley said.

To help make up the deficit, the American Cancer Society will double its research budget to $240 million by 2021, he added.

But Dr. Grupp notes that charities and the drug industry are often reluctant to cover the indirect costs of research, such as labs. Without steady, predictable support from government grants, Dr. Grupp said he wouldn’t “have a building to do my research in or a way to keep the lights on.”


 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Less and less of the research presented at a prominent cancer conference is supported by the National Institutes of Health, a development that some of the country’s top scientists see as a worrisome trend.

The number of studies fully funded by the NIH at the annual meeting of the American Society of Clinical Oncology (ASCO) – the world’s largest gathering of cancer researchers – has fallen 75% in the past decade, from 575 papers in 2008 to 144 this year, according to the society, which meets June 2-6 in Chicago.

American researchers typically dominate the meeting’s press conferences – designed to feature the most important and newsworthy research. This year, there are 14 studies led by international scientists versus 12 led by U.S.-based research teams. That’s a big shift from just 5 years ago, when 15 studies in the “press program” were led by Americans versus 9 by international researchers.

Several of the studies on this weekend’s press program come from Europe and Canada, along with two from China.

President Donald Trump has proposed cutting the NIH budget for 2018 from $31.8 billion to $26 billion, a decline that many worry would jeopardize the fight against cancer and other diseases. Those cuts include $1 billion less for the National Cancer Institute.

On its website, the NCI notes that its purchasing power already has declined by 25% since 2003, because its budget – while growing – hasn’t kept up with inflation. Congress gave the NCI nearly $5.4 billion in fiscal year 2017, an increase of $174.6 million over last year. The NCI also received $300 million for the Beau Biden Cancer Moonshot through the 21st Century Cures Act in December 2016.

“America may be losing its edge in medical research,” said Otis Brawley, MD, chief medical officer at the American Cancer Society. The brightest young scientists are having trouble finding funding for their research, leading them to look for jobs not at universities but at drug companies “or even Wall Street,” he said. “I fear we are losing a generation of young, talented biomedical scientists.”

Some see America’s leading role in science as a point of national pride.

“Do we want the U.S. to remain at the center of biomedical innovation, or do we want to cede that to China or other countries?” said Dr. Stephan Grupp, director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia. “If you don’t push to stay in front, you don’t stay in front.”

But more than pride is at stake.

Public funding is critical, because it allows researchers to answer questions that don’t interest drug companies, said Richard Schilsky, senior vice president and chief medical officer at ASCO.

While drug companies fund studies that help them get their medications approved, they tend not to pay for studies that focus on cancer prevention, screening, or quality of life, Mr. Schilsky said. The NIH also funds head-to-head comparisons of cancer drugs, which allow patients and doctors to select the most effective treatments.

“If the NIH-funded studies continue to decline, we simply won’t get the answers that patients are looking for,” he said.

While government research often addresses areas of greatest need, “industry research is geared toward marketable products,” Dr. Brawley said.

To help make up the deficit, the American Cancer Society will double its research budget to $240 million by 2021, he added.

But Dr. Grupp notes that charities and the drug industry are often reluctant to cover the indirect costs of research, such as labs. Without steady, predictable support from government grants, Dr. Grupp said he wouldn’t “have a building to do my research in or a way to keep the lights on.”


 

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Zika virus infection has been occurring in pregnant women at a slow but steady clip over the last couple of months, but cases of liveborn infants with Zika-related birth defects have jumped in recent weeks, according to the Centers for Disease Control and Prevention.

Eight liveborn infants with Zika-related birth defects were reported to the U.S. Zika Pregnancy Registry during the 2 weeks ending May 23, more than any other 2-week period this year, and that was after six such infants were reported for the 2 weeks ending May 9. The total for the 50 states and the District of Columbia is now 72 for 2016-2017. No new pregnancy losses with birth defects were reported over the same 4-week span, so the 50 state/D.C. total remained at eight for 2016-2017, CDC data show.

[email protected]

Zika virus infection has been occurring in pregnant women at a slow but steady clip over the last couple of months, but cases of liveborn infants with Zika-related birth defects have jumped in recent weeks, according to the Centers for Disease Control and Prevention.

Eight liveborn infants with Zika-related birth defects were reported to the U.S. Zika Pregnancy Registry during the 2 weeks ending May 23, more than any other 2-week period this year, and that was after six such infants were reported for the 2 weeks ending May 9. The total for the 50 states and the District of Columbia is now 72 for 2016-2017. No new pregnancy losses with birth defects were reported over the same 4-week span, so the 50 state/D.C. total remained at eight for 2016-2017, CDC data show.

[email protected]

Zika virus infection has been occurring in pregnant women at a slow but steady clip over the last couple of months, but cases of liveborn infants with Zika-related birth defects have jumped in recent weeks, according to the Centers for Disease Control and Prevention.

Eight liveborn infants with Zika-related birth defects were reported to the U.S. Zika Pregnancy Registry during the 2 weeks ending May 23, more than any other 2-week period this year, and that was after six such infants were reported for the 2 weeks ending May 9. The total for the 50 states and the District of Columbia is now 72 for 2016-2017. No new pregnancy losses with birth defects were reported over the same 4-week span, so the 50 state/D.C. total remained at eight for 2016-2017, CDC data show.

[email protected]

Maintenance of Certification (MOC) was adopted by the 24 certifying boards constituting the American Board of Medical Specialties (ABMS) in 2000. The American Board of Dermatology (ABD) granted its first time-limited certificates in 1991 with the first cohort of diplomates entering MOC in 2006. The rationale for MOC centered on 2 propositions: First, continuing medical education (CME) alone was insufficient to assure the public that physicians were remaining up-to-date with an expanding knowledge base and offered little opportunity to engage in meaningful self-assessment and practice improvement. Second, parties external to the medical profession were focusing increased attention on physician error and quality assurance in medical practice. Maintenance of Certification, therefore, provided a mechanism of physician self-regulation in meeting public scrutiny.^1,2

The basic framework of MOC remains unchanged since its inception, though notable effort has been expended in simplifying the tools available. All MOC components offered directly by ABD including the MOC examination are covered by the $150 annual fee.

Professional Standing

Diplomates attest to the status of all state medical licenses and level of clinical activity. All licenses must be unrestricted. “Clinically active” is defined as any patient care delivered within the prior 12 months. Having a restricted license or being clinically inactive does not automatically trigger loss of certification but does result in an ABD review.

Self-assessment

Diplomates complete 300 credits (1 question=1 credit) over 10 years and complete, or attest to prior completion of, a foundational course in patient safety. Self-assessment questions are widely available from various sources, including the Question of the Week offered by the American Academy of Dermatology, Clinicopathologic Correlation and CME-designated articles offered by JAMA Dermatology, and Photo Challenges and Dermatopathology Diagnosis quizzes offered by Cutis. The ABD recognizes patient safety education satisfied as part of medical school and residency as well as various other venues. Online courses offering CME and MOC credit also are available. Credit is accrued whether the item is answered correctly or not.

Cognitive Expertise

Dermatologists take a general dermatology module and choose one subspecialty module composed of questions directed to the clinical practitioner. The general module consists of 100 image items, most of which ask for a diagnosis. The list of entities potentially included on the assessment is made available in advance for self-study. The subspecialty module consists of 50 questions targeting the specific content area selected: medical dermatology, surgical dermatology, pediatric dermatology, and dermatopathology. The actual questions also are made available in advance for self-study. Board-certified pediatric dermatologists and dermatopathologists are offered a second 50-question set of items in their specialty to allow maintenance of the second certificate. Venues include Pearson VUE testing centers and at-home or in-office tests by remote proctoring.

The ABD is considering participation in the longitudinal assessment program developed by the ABMS. If adopted, it will offer questions distributed over a many-year span in small packets, on mobile devices, and on personal computers. Diplomates will have the ability to select content and pace, including opt-out periods as life events dictate. A minimum number of correctly answered items over time will form the basis for summative assessment.

Practice Improvement

A critical element of MOC, practice improvement affords the physician the opportunity to study how patients receive care in a wide range of settings. Beginning in 2015, the ABD developed focused practice improvement modules, now totaling 21, with many more coming in the future. The free modules are offered on an online platform (https://secure.dataharborsolutions.com/ABDermOrg/Default.aspx) and target narrow content areas. The broad range of offerings allows diplomates to choose an area of specific interest. The participant is asked to read an overview and rationale for the module, consider reading selected references that provide the evidence base, and perform 5 chart abstractions consisting of yes or no answers to no more than 5 questions narrowly focused on the chosen topic. If a first round shows no room for improvement, the participant is finished. If a deficiency is identified, the diplomate can reflect on and implement any necessary changes in process of care and pursue a second round. These modules have been very well received, with typical diplomates’ comments expressing appreciation for the ease of use and relevance to practice. Unedited and unselected reviews can be found online (https://www.abderm.org/diplomates/fulfilling-moc-requirements/resource-vendor-list/practice-improvement/american-board-of-dermatology-focused-pi-modules-free.aspx).

Future Direction

The ABD continuously communicates with diplomates about changes and new opportunities in its MOC program with a goal of maximizing value and minimizing cost in terms of dollars and time.³ The directors of the ABD continue to seek feedback about the MOC program and are committed to further refinements to achieve this goal. A critical feature of the redesigned website (http://www.abderm.org/) allows diplomates to submit and read anonymous reviews of all tools available to fulfill MOC requirements. This thoughtful diplomate feedback informs MOC developmental efforts.

All directors and executive staff of the ABD, regardless of certificate status, pay the annual fee and participate in MOC. Active participation in MOC is made public on the ABMS website. This acknowledgment is an assurance to patients that the physician’s professional standing is sound, that the physician periodically self-assesses what he/she knows, that this knowledge meets psychometrically valid standards set by dermatologists, and that physicians explore the quality of care delivered in specific practice settings. It’s the right thing to do!

Maintenance of Certification (MOC) was adopted by the 24 certifying boards constituting the American Board of Medical Specialties (ABMS) in 2000. The American Board of Dermatology (ABD) granted its first time-limited certificates in 1991 with the first cohort of diplomates entering MOC in 2006. The rationale for MOC centered on 2 propositions: First, continuing medical education (CME) alone was insufficient to assure the public that physicians were remaining up-to-date with an expanding knowledge base and offered little opportunity to engage in meaningful self-assessment and practice improvement. Second, parties external to the medical profession were focusing increased attention on physician error and quality assurance in medical practice. Maintenance of Certification, therefore, provided a mechanism of physician self-regulation in meeting public scrutiny.^1,2

The basic framework of MOC remains unchanged since its inception, though notable effort has been expended in simplifying the tools available. All MOC components offered directly by ABD including the MOC examination are covered by the $150 annual fee.

Professional Standing

Diplomates attest to the status of all state medical licenses and level of clinical activity. All licenses must be unrestricted. “Clinically active” is defined as any patient care delivered within the prior 12 months. Having a restricted license or being clinically inactive does not automatically trigger loss of certification but does result in an ABD review.

Self-assessment

Diplomates complete 300 credits (1 question=1 credit) over 10 years and complete, or attest to prior completion of, a foundational course in patient safety. Self-assessment questions are widely available from various sources, including the Question of the Week offered by the American Academy of Dermatology, Clinicopathologic Correlation and CME-designated articles offered by JAMA Dermatology, and Photo Challenges and Dermatopathology Diagnosis quizzes offered by Cutis. The ABD recognizes patient safety education satisfied as part of medical school and residency as well as various other venues. Online courses offering CME and MOC credit also are available. Credit is accrued whether the item is answered correctly or not.

Cognitive Expertise

Dermatologists take a general dermatology module and choose one subspecialty module composed of questions directed to the clinical practitioner. The general module consists of 100 image items, most of which ask for a diagnosis. The list of entities potentially included on the assessment is made available in advance for self-study. The subspecialty module consists of 50 questions targeting the specific content area selected: medical dermatology, surgical dermatology, pediatric dermatology, and dermatopathology. The actual questions also are made available in advance for self-study. Board-certified pediatric dermatologists and dermatopathologists are offered a second 50-question set of items in their specialty to allow maintenance of the second certificate. Venues include Pearson VUE testing centers and at-home or in-office tests by remote proctoring.

The ABD is considering participation in the longitudinal assessment program developed by the ABMS. If adopted, it will offer questions distributed over a many-year span in small packets, on mobile devices, and on personal computers. Diplomates will have the ability to select content and pace, including opt-out periods as life events dictate. A minimum number of correctly answered items over time will form the basis for summative assessment.

Practice Improvement

A critical element of MOC, practice improvement affords the physician the opportunity to study how patients receive care in a wide range of settings. Beginning in 2015, the ABD developed focused practice improvement modules, now totaling 21, with many more coming in the future. The free modules are offered on an online platform (https://secure.dataharborsolutions.com/ABDermOrg/Default.aspx) and target narrow content areas. The broad range of offerings allows diplomates to choose an area of specific interest. The participant is asked to read an overview and rationale for the module, consider reading selected references that provide the evidence base, and perform 5 chart abstractions consisting of yes or no answers to no more than 5 questions narrowly focused on the chosen topic. If a first round shows no room for improvement, the participant is finished. If a deficiency is identified, the diplomate can reflect on and implement any necessary changes in process of care and pursue a second round. These modules have been very well received, with typical diplomates’ comments expressing appreciation for the ease of use and relevance to practice. Unedited and unselected reviews can be found online (https://www.abderm.org/diplomates/fulfilling-moc-requirements/resource-vendor-list/practice-improvement/american-board-of-dermatology-focused-pi-modules-free.aspx).

Future Direction

The ABD continuously communicates with diplomates about changes and new opportunities in its MOC program with a goal of maximizing value and minimizing cost in terms of dollars and time.³ The directors of the ABD continue to seek feedback about the MOC program and are committed to further refinements to achieve this goal. A critical feature of the redesigned website (http://www.abderm.org/) allows diplomates to submit and read anonymous reviews of all tools available to fulfill MOC requirements. This thoughtful diplomate feedback informs MOC developmental efforts.

All directors and executive staff of the ABD, regardless of certificate status, pay the annual fee and participate in MOC. Active participation in MOC is made public on the ABMS website. This acknowledgment is an assurance to patients that the physician’s professional standing is sound, that the physician periodically self-assesses what he/she knows, that this knowledge meets psychometrically valid standards set by dermatologists, and that physicians explore the quality of care delivered in specific practice settings. It’s the right thing to do!

Maintenance of Certification (MOC) was adopted by the 24 certifying boards constituting the American Board of Medical Specialties (ABMS) in 2000. The American Board of Dermatology (ABD) granted its first time-limited certificates in 1991 with the first cohort of diplomates entering MOC in 2006. The rationale for MOC centered on 2 propositions: First, continuing medical education (CME) alone was insufficient to assure the public that physicians were remaining up-to-date with an expanding knowledge base and offered little opportunity to engage in meaningful self-assessment and practice improvement. Second, parties external to the medical profession were focusing increased attention on physician error and quality assurance in medical practice. Maintenance of Certification, therefore, provided a mechanism of physician self-regulation in meeting public scrutiny.^1,2

The basic framework of MOC remains unchanged since its inception, though notable effort has been expended in simplifying the tools available. All MOC components offered directly by ABD including the MOC examination are covered by the $150 annual fee.

Professional Standing

Diplomates attest to the status of all state medical licenses and level of clinical activity. All licenses must be unrestricted. “Clinically active” is defined as any patient care delivered within the prior 12 months. Having a restricted license or being clinically inactive does not automatically trigger loss of certification but does result in an ABD review.

Self-assessment

Diplomates complete 300 credits (1 question=1 credit) over 10 years and complete, or attest to prior completion of, a foundational course in patient safety. Self-assessment questions are widely available from various sources, including the Question of the Week offered by the American Academy of Dermatology, Clinicopathologic Correlation and CME-designated articles offered by JAMA Dermatology, and Photo Challenges and Dermatopathology Diagnosis quizzes offered by Cutis. The ABD recognizes patient safety education satisfied as part of medical school and residency as well as various other venues. Online courses offering CME and MOC credit also are available. Credit is accrued whether the item is answered correctly or not.

Cognitive Expertise

Dermatologists take a general dermatology module and choose one subspecialty module composed of questions directed to the clinical practitioner. The general module consists of 100 image items, most of which ask for a diagnosis. The list of entities potentially included on the assessment is made available in advance for self-study. The subspecialty module consists of 50 questions targeting the specific content area selected: medical dermatology, surgical dermatology, pediatric dermatology, and dermatopathology. The actual questions also are made available in advance for self-study. Board-certified pediatric dermatologists and dermatopathologists are offered a second 50-question set of items in their specialty to allow maintenance of the second certificate. Venues include Pearson VUE testing centers and at-home or in-office tests by remote proctoring.

The ABD is considering participation in the longitudinal assessment program developed by the ABMS. If adopted, it will offer questions distributed over a many-year span in small packets, on mobile devices, and on personal computers. Diplomates will have the ability to select content and pace, including opt-out periods as life events dictate. A minimum number of correctly answered items over time will form the basis for summative assessment.

Practice Improvement

A critical element of MOC, practice improvement affords the physician the opportunity to study how patients receive care in a wide range of settings. Beginning in 2015, the ABD developed focused practice improvement modules, now totaling 21, with many more coming in the future. The free modules are offered on an online platform (https://secure.dataharborsolutions.com/ABDermOrg/Default.aspx) and target narrow content areas. The broad range of offerings allows diplomates to choose an area of specific interest. The participant is asked to read an overview and rationale for the module, consider reading selected references that provide the evidence base, and perform 5 chart abstractions consisting of yes or no answers to no more than 5 questions narrowly focused on the chosen topic. If a first round shows no room for improvement, the participant is finished. If a deficiency is identified, the diplomate can reflect on and implement any necessary changes in process of care and pursue a second round. These modules have been very well received, with typical diplomates’ comments expressing appreciation for the ease of use and relevance to practice. Unedited and unselected reviews can be found online (https://www.abderm.org/diplomates/fulfilling-moc-requirements/resource-vendor-list/practice-improvement/american-board-of-dermatology-focused-pi-modules-free.aspx).

Future Direction

The ABD continuously communicates with diplomates about changes and new opportunities in its MOC program with a goal of maximizing value and minimizing cost in terms of dollars and time.³ The directors of the ABD continue to seek feedback about the MOC program and are committed to further refinements to achieve this goal. A critical feature of the redesigned website (http://www.abderm.org/) allows diplomates to submit and read anonymous reviews of all tools available to fulfill MOC requirements. This thoughtful diplomate feedback informs MOC developmental efforts.

All directors and executive staff of the ABD, regardless of certificate status, pay the annual fee and participate in MOC. Active participation in MOC is made public on the ABMS website. This acknowledgment is an assurance to patients that the physician’s professional standing is sound, that the physician periodically self-assesses what he/she knows, that this knowledge meets psychometrically valid standards set by dermatologists, and that physicians explore the quality of care delivered in specific practice settings. It’s the right thing to do!

Let me ask you a question: When was the last time you used the Krebs cycle in the hospital?

Now another question: When did you last have to persuade your boss to give you additional resources?

My guess is that your need for additional resources comes up more frequently than the Krebs cycle. It’s interesting that we spent so much time in our training focused on biochemical pathways and next to nothing on leadership skills, such as ways to motivate our health care teams or the most effective way to provide feedback – skills that we use on a regular basis. Yet, these skills are just as critical as understanding the science behind our daily work.

1. Highlight the importance of the ask.

2. Leverage data to prove the point.

3. Illustrate large-scale implications of the ask.

4. Make the ask.

I’ll use a project to increase DVT prophylaxis rates to illustrate this point:

1. Highlight the importance of DVT prophylaxis: I would focus on statistics that would surprise the audience, such as “Hospital acquired venous thromboembolism leads to significant morbidity and mortality, including more than 100,000 deaths.”¹

2. Leverage data to prove the point: “Worldwide, only 40%-60% of patients who require DVT prophylaxis actually receive it in the hospital.² Our performance leaves tremendous room for improvement – we’re currently at 68%.”

3. Illustrate large-scale implications of the ask: “If we do this, it enhances our reputation as a group, and it will improve hospital revenues.”

4. Make the ask: “I have an evidence-based protocol that we need to implement to achieve results.”

Through leadership courses over the past couple of years, I’ve changed my approach significantly. By leveraging concepts from behavioral economics, we can significantly improve the effect of our work. Here’s how I would conduct that same meeting:

1. Connect with the audience in a genuine way: Start off with “You are quality-minded providers who have taken on major challenges in the past and successfully delivered results, like the time you reduced the rates of catheter associated urinary tract infections.”

2. Make the ask: “I’m here to talk to you about improving our DVT prophylaxis rates. Here’s the protocol we need to implement.”

3. Leverage data to prove the point: “DVT prophylaxis rates at the hospital across town (or at another unit in the hospital) are at 82%. What do you think our numbers are? We’re actually at 68%!”

4. Illustrate large-scale implications of the ask: “We all know this. Patients under our care will die or be seriously harmed if we don’t improve our practice. The hospital will also lose money, which will ultimately impact us. So, we have two options: a) We can continue what we’ve been doing – work as hard as we can and our practice will not improve. b) Or we can decide today to pilot this new protocol and change our practice and performance.”

Let’s look at the changes above in greater detail:

Connect with the audience in a genuine way: Instead of highlighting the importance of the ask with statistics, use an attention getter to connect with the group. Highlighting the fact that the group is “quality-minded” and has surmounted challenging obstacles in the past reinforces the providers’ sense of identity.³ This helps the group think more openly about the proposal.

Make the ask: Now that you’ve captured their attention, make your ask, clearly and concisely, upfront. Remember, in today’s health care settings, we have short attention spans. You’re minutes away from someone getting paged away from the meeting or people checking their emails or the latest Facebook post. Don’t schedule the protocol review as the last item on the agenda.

Leverage data to prove your point: Data are powerful, but only if presented in the right way. Use questions to keep your audience engaged (“What do you think our numbers are?”), particularly around data, where most people decide to switch their attention to their smartphones. Based on your access to data sources, find another unit or institution with a higher performance than yours. State that upfront. It anchors,the group to a higher number, so, when you reveal your current performance, the gap is highlighted. ^3,4 In the first case, when the lower national average of 40-60% is presented initially, the group will be happy that their performance is in fact better at 68%.

Illustrate large-scale implications of the ask: There are two concepts at work here: First, loss aversion.^3,4 We tend to experience greater psychological burden with losses versus gains. Changing the framing from the fact that the hospital will lose money, versus making money in the first case, changes how we perceive the information. Second, active choice.³ Emphasizing that a decision has to be made today and giving the group a choice around it increases the likelihood of walking out of the meeting with a decision.

With some simple, yet thoughtful, modifications, the message takes on a more effective tone, and, based on my experience, it is significantly more impactful.

So, while I’m a fan of biochemical pathways that enable us to generate energy, I also hope we can integrate leadership lessons into our day-to-day learning and life.

Dr. Afsar is an assistant clinical professor in the departments of medicine and neurosurgery and the associate chief medical officer at UCLA Hospitals.

References

1. The Surgeon General’s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Office of the Surgeon General (US); National Heart, Lung, and Blood Institute (US). Office of the Surgeon General (US). 2008.

2. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): A multinational cross-sectional study. Lancet. 2008;371(9610):387-94.

3. Soman D. The Last Mile. 2015.

4. Thaler RH, Sunstein CR. Nudge. 2009.

Let me ask you a question: When was the last time you used the Krebs cycle in the hospital?

Now another question: When did you last have to persuade your boss to give you additional resources?

My guess is that your need for additional resources comes up more frequently than the Krebs cycle. It’s interesting that we spent so much time in our training focused on biochemical pathways and next to nothing on leadership skills, such as ways to motivate our health care teams or the most effective way to provide feedback – skills that we use on a regular basis. Yet, these skills are just as critical as understanding the science behind our daily work.

1. Highlight the importance of the ask.

2. Leverage data to prove the point.

3. Illustrate large-scale implications of the ask.

4. Make the ask.

I’ll use a project to increase DVT prophylaxis rates to illustrate this point:

1. Highlight the importance of DVT prophylaxis: I would focus on statistics that would surprise the audience, such as “Hospital acquired venous thromboembolism leads to significant morbidity and mortality, including more than 100,000 deaths.”¹

2. Leverage data to prove the point: “Worldwide, only 40%-60% of patients who require DVT prophylaxis actually receive it in the hospital.² Our performance leaves tremendous room for improvement – we’re currently at 68%.”

3. Illustrate large-scale implications of the ask: “If we do this, it enhances our reputation as a group, and it will improve hospital revenues.”

4. Make the ask: “I have an evidence-based protocol that we need to implement to achieve results.”

Through leadership courses over the past couple of years, I’ve changed my approach significantly. By leveraging concepts from behavioral economics, we can significantly improve the effect of our work. Here’s how I would conduct that same meeting:

1. Connect with the audience in a genuine way: Start off with “You are quality-minded providers who have taken on major challenges in the past and successfully delivered results, like the time you reduced the rates of catheter associated urinary tract infections.”

2. Make the ask: “I’m here to talk to you about improving our DVT prophylaxis rates. Here’s the protocol we need to implement.”

3. Leverage data to prove the point: “DVT prophylaxis rates at the hospital across town (or at another unit in the hospital) are at 82%. What do you think our numbers are? We’re actually at 68%!”

4. Illustrate large-scale implications of the ask: “We all know this. Patients under our care will die or be seriously harmed if we don’t improve our practice. The hospital will also lose money, which will ultimately impact us. So, we have two options: a) We can continue what we’ve been doing – work as hard as we can and our practice will not improve. b) Or we can decide today to pilot this new protocol and change our practice and performance.”

Let’s look at the changes above in greater detail:

Connect with the audience in a genuine way: Instead of highlighting the importance of the ask with statistics, use an attention getter to connect with the group. Highlighting the fact that the group is “quality-minded” and has surmounted challenging obstacles in the past reinforces the providers’ sense of identity.³ This helps the group think more openly about the proposal.

Make the ask: Now that you’ve captured their attention, make your ask, clearly and concisely, upfront. Remember, in today’s health care settings, we have short attention spans. You’re minutes away from someone getting paged away from the meeting or people checking their emails or the latest Facebook post. Don’t schedule the protocol review as the last item on the agenda.

Leverage data to prove your point: Data are powerful, but only if presented in the right way. Use questions to keep your audience engaged (“What do you think our numbers are?”), particularly around data, where most people decide to switch their attention to their smartphones. Based on your access to data sources, find another unit or institution with a higher performance than yours. State that upfront. It anchors,the group to a higher number, so, when you reveal your current performance, the gap is highlighted. ^3,4 In the first case, when the lower national average of 40-60% is presented initially, the group will be happy that their performance is in fact better at 68%.

Illustrate large-scale implications of the ask: There are two concepts at work here: First, loss aversion.^3,4 We tend to experience greater psychological burden with losses versus gains. Changing the framing from the fact that the hospital will lose money, versus making money in the first case, changes how we perceive the information. Second, active choice.³ Emphasizing that a decision has to be made today and giving the group a choice around it increases the likelihood of walking out of the meeting with a decision.

With some simple, yet thoughtful, modifications, the message takes on a more effective tone, and, based on my experience, it is significantly more impactful.

So, while I’m a fan of biochemical pathways that enable us to generate energy, I also hope we can integrate leadership lessons into our day-to-day learning and life.

Dr. Afsar is an assistant clinical professor in the departments of medicine and neurosurgery and the associate chief medical officer at UCLA Hospitals.

References

1. The Surgeon General’s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Office of the Surgeon General (US); National Heart, Lung, and Blood Institute (US). Office of the Surgeon General (US). 2008.

2. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): A multinational cross-sectional study. Lancet. 2008;371(9610):387-94.

3. Soman D. The Last Mile. 2015.

4. Thaler RH, Sunstein CR. Nudge. 2009.

Let me ask you a question: When was the last time you used the Krebs cycle in the hospital?

Now another question: When did you last have to persuade your boss to give you additional resources?

My guess is that your need for additional resources comes up more frequently than the Krebs cycle. It’s interesting that we spent so much time in our training focused on biochemical pathways and next to nothing on leadership skills, such as ways to motivate our health care teams or the most effective way to provide feedback – skills that we use on a regular basis. Yet, these skills are just as critical as understanding the science behind our daily work.

1. Highlight the importance of the ask.

2. Leverage data to prove the point.

3. Illustrate large-scale implications of the ask.

4. Make the ask.

I’ll use a project to increase DVT prophylaxis rates to illustrate this point:

1. Highlight the importance of DVT prophylaxis: I would focus on statistics that would surprise the audience, such as “Hospital acquired venous thromboembolism leads to significant morbidity and mortality, including more than 100,000 deaths.”¹

2. Leverage data to prove the point: “Worldwide, only 40%-60% of patients who require DVT prophylaxis actually receive it in the hospital.² Our performance leaves tremendous room for improvement – we’re currently at 68%.”

3. Illustrate large-scale implications of the ask: “If we do this, it enhances our reputation as a group, and it will improve hospital revenues.”

4. Make the ask: “I have an evidence-based protocol that we need to implement to achieve results.”

Through leadership courses over the past couple of years, I’ve changed my approach significantly. By leveraging concepts from behavioral economics, we can significantly improve the effect of our work. Here’s how I would conduct that same meeting:

1. Connect with the audience in a genuine way: Start off with “You are quality-minded providers who have taken on major challenges in the past and successfully delivered results, like the time you reduced the rates of catheter associated urinary tract infections.”

2. Make the ask: “I’m here to talk to you about improving our DVT prophylaxis rates. Here’s the protocol we need to implement.”

3. Leverage data to prove the point: “DVT prophylaxis rates at the hospital across town (or at another unit in the hospital) are at 82%. What do you think our numbers are? We’re actually at 68%!”

4. Illustrate large-scale implications of the ask: “We all know this. Patients under our care will die or be seriously harmed if we don’t improve our practice. The hospital will also lose money, which will ultimately impact us. So, we have two options: a) We can continue what we’ve been doing – work as hard as we can and our practice will not improve. b) Or we can decide today to pilot this new protocol and change our practice and performance.”

Let’s look at the changes above in greater detail:

Connect with the audience in a genuine way: Instead of highlighting the importance of the ask with statistics, use an attention getter to connect with the group. Highlighting the fact that the group is “quality-minded” and has surmounted challenging obstacles in the past reinforces the providers’ sense of identity.³ This helps the group think more openly about the proposal.

Make the ask: Now that you’ve captured their attention, make your ask, clearly and concisely, upfront. Remember, in today’s health care settings, we have short attention spans. You’re minutes away from someone getting paged away from the meeting or people checking their emails or the latest Facebook post. Don’t schedule the protocol review as the last item on the agenda.

Leverage data to prove your point: Data are powerful, but only if presented in the right way. Use questions to keep your audience engaged (“What do you think our numbers are?”), particularly around data, where most people decide to switch their attention to their smartphones. Based on your access to data sources, find another unit or institution with a higher performance than yours. State that upfront. It anchors,the group to a higher number, so, when you reveal your current performance, the gap is highlighted. ^3,4 In the first case, when the lower national average of 40-60% is presented initially, the group will be happy that their performance is in fact better at 68%.

Illustrate large-scale implications of the ask: There are two concepts at work here: First, loss aversion.^3,4 We tend to experience greater psychological burden with losses versus gains. Changing the framing from the fact that the hospital will lose money, versus making money in the first case, changes how we perceive the information. Second, active choice.³ Emphasizing that a decision has to be made today and giving the group a choice around it increases the likelihood of walking out of the meeting with a decision.

With some simple, yet thoughtful, modifications, the message takes on a more effective tone, and, based on my experience, it is significantly more impactful.

So, while I’m a fan of biochemical pathways that enable us to generate energy, I also hope we can integrate leadership lessons into our day-to-day learning and life.

Dr. Afsar is an assistant clinical professor in the departments of medicine and neurosurgery and the associate chief medical officer at UCLA Hospitals.

References

1. The Surgeon General’s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Office of the Surgeon General (US); National Heart, Lung, and Blood Institute (US). Office of the Surgeon General (US). 2008.

2. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): A multinational cross-sectional study. Lancet. 2008;371(9610):387-94.

3. Soman D. The Last Mile. 2015.

4. Thaler RH, Sunstein CR. Nudge. 2009.

Currently, there is no widely accepted tool for assessing the severity of psoriasis in the clinical setting.^1-5 Moreover, there is still a need for a simple assessment tool to assist in evaluating a patient’s response to therapy in clinical practice.⁶

The body surface area (BSA) is a familiar and widely used measurement by clinicians. It is easily calculated by the rule of nines or with the patient’s open palm and thumb approximating 1% of the BSA.⁷ Body surface area is an uncomplicated concept for patients to understand and interpret. It also promotes patient empowerment and self-care by allowing patients to monitor short-term and long-term response to therapy.

The National Psoriasis Foundation Medical Board published treatment targets for plaque psoriasis. One of the conclusions states, “The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline.”⁸

We propose a new nomenclature that a 75% improvement in BSA be recognized as BSA75, a 90% improvement in BSA as BSA90, and a 100% improvement in BSA as BSA100. These classifications would be analogous to corresponding improvements in the following psoriasis area and severity index (PASI) scores: PASI 75, PASI 90, PASI 100.⁹ A loss of BSA goals/milestones (ie, BSA75) could encourage and facilitate physician-patient conversations and further direct modifications to disease management and treatment therapy.

A potential drawback to the implementation of this novel categorization system is that other notable aspects of psoriasis would not be assessed, such as erythema, induration, or scale; subjective measurements; patient quality of life; patient symptoms; areas of involvement (eg, palms, soles of feet); and disease course. Nevertheless, the BSA75, BSA90, and BSA100 classifications can serve as practical, objective, and straightforward tools to monitor disease progression and treatment response in psoriasis patients, which may potentially promote improved patient outcomes in clinical practice.

Currently, there is no widely accepted tool for assessing the severity of psoriasis in the clinical setting.^1-5 Moreover, there is still a need for a simple assessment tool to assist in evaluating a patient’s response to therapy in clinical practice.⁶

The body surface area (BSA) is a familiar and widely used measurement by clinicians. It is easily calculated by the rule of nines or with the patient’s open palm and thumb approximating 1% of the BSA.⁷ Body surface area is an uncomplicated concept for patients to understand and interpret. It also promotes patient empowerment and self-care by allowing patients to monitor short-term and long-term response to therapy.

The National Psoriasis Foundation Medical Board published treatment targets for plaque psoriasis. One of the conclusions states, “The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline.”⁸

We propose a new nomenclature that a 75% improvement in BSA be recognized as BSA75, a 90% improvement in BSA as BSA90, and a 100% improvement in BSA as BSA100. These classifications would be analogous to corresponding improvements in the following psoriasis area and severity index (PASI) scores: PASI 75, PASI 90, PASI 100.⁹ A loss of BSA goals/milestones (ie, BSA75) could encourage and facilitate physician-patient conversations and further direct modifications to disease management and treatment therapy.

A potential drawback to the implementation of this novel categorization system is that other notable aspects of psoriasis would not be assessed, such as erythema, induration, or scale; subjective measurements; patient quality of life; patient symptoms; areas of involvement (eg, palms, soles of feet); and disease course. Nevertheless, the BSA75, BSA90, and BSA100 classifications can serve as practical, objective, and straightforward tools to monitor disease progression and treatment response in psoriasis patients, which may potentially promote improved patient outcomes in clinical practice.

Currently, there is no widely accepted tool for assessing the severity of psoriasis in the clinical setting.^1-5 Moreover, there is still a need for a simple assessment tool to assist in evaluating a patient’s response to therapy in clinical practice.⁶

The body surface area (BSA) is a familiar and widely used measurement by clinicians. It is easily calculated by the rule of nines or with the patient’s open palm and thumb approximating 1% of the BSA.⁷ Body surface area is an uncomplicated concept for patients to understand and interpret. It also promotes patient empowerment and self-care by allowing patients to monitor short-term and long-term response to therapy.

The National Psoriasis Foundation Medical Board published treatment targets for plaque psoriasis. One of the conclusions states, “The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline.”⁸

We propose a new nomenclature that a 75% improvement in BSA be recognized as BSA75, a 90% improvement in BSA as BSA90, and a 100% improvement in BSA as BSA100. These classifications would be analogous to corresponding improvements in the following psoriasis area and severity index (PASI) scores: PASI 75, PASI 90, PASI 100.⁹ A loss of BSA goals/milestones (ie, BSA75) could encourage and facilitate physician-patient conversations and further direct modifications to disease management and treatment therapy.

A potential drawback to the implementation of this novel categorization system is that other notable aspects of psoriasis would not be assessed, such as erythema, induration, or scale; subjective measurements; patient quality of life; patient symptoms; areas of involvement (eg, palms, soles of feet); and disease course. Nevertheless, the BSA75, BSA90, and BSA100 classifications can serve as practical, objective, and straightforward tools to monitor disease progression and treatment response in psoriasis patients, which may potentially promote improved patient outcomes in clinical practice.

SAN FRANCISCO – Pediatric patients who have asthma that is poorly controlled may be more likely to have functional gastrointestinal (GI) disorders, which feature chronic GI distress that has several causes, according to a study of patients treated at one hospital.

Female sex and increased anxiety were influential factors.

“This study suggests a high prevalence of functional GI disorders among patients with persistent asthma. Moreover, patients with functional GI disorders had poor asthma control and increased anxiety. Clinicians should consider functional GI disorders in patients with poor asthma control and assess for anxiety as indicated,” Ruben J. Colman, MD, a pediatric resident at SBH Health System, Bronx, N.Y., said at the Pediatric Academic Societies meeting.

Louis-Paul St-Onge/iStockphoto

SAN FRANCISCO – Pediatric patients who have asthma that is poorly controlled may be more likely to have functional gastrointestinal (GI) disorders, which feature chronic GI distress that has several causes, according to a study of patients treated at one hospital.

Female sex and increased anxiety were influential factors.

“This study suggests a high prevalence of functional GI disorders among patients with persistent asthma. Moreover, patients with functional GI disorders had poor asthma control and increased anxiety. Clinicians should consider functional GI disorders in patients with poor asthma control and assess for anxiety as indicated,” Ruben J. Colman, MD, a pediatric resident at SBH Health System, Bronx, N.Y., said at the Pediatric Academic Societies meeting.

Louis-Paul St-Onge/iStockphoto

SAN FRANCISCO – Pediatric patients who have asthma that is poorly controlled may be more likely to have functional gastrointestinal (GI) disorders, which feature chronic GI distress that has several causes, according to a study of patients treated at one hospital.

Female sex and increased anxiety were influential factors.

“This study suggests a high prevalence of functional GI disorders among patients with persistent asthma. Moreover, patients with functional GI disorders had poor asthma control and increased anxiety. Clinicians should consider functional GI disorders in patients with poor asthma control and assess for anxiety as indicated,” Ruben J. Colman, MD, a pediatric resident at SBH Health System, Bronx, N.Y., said at the Pediatric Academic Societies meeting.

Louis-Paul St-Onge/iStockphoto

multiple myeloma

A team of researchers has confirmed that minimal residual disease (MRD) negativity is superior to complete response (CR) as a prognostic marker for progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma (MM).

MRD-positive patients who achieved CR had a similar survival to MRD-positive patients who achieved near CR (nCR) or partial response (PR). And this held true despite different induction regimens, disease stages, patient ages, cytogenetic groups, and whether the patients were transplant eligible or ineligible.

The team conducted the pooled analysis on behalf of the GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group.

They analyzed data from a large pool of 609 patients newly diagnosed with MM enrolled in 3 clinical trials—GEM 2000 (n=256), GEM2005MENOS65 (n=226), and GEM2010MAS65 (n=127). All patients had MRD assessments 9 months after study enrollment. The median follow-up was 71 months.

Juan-Jose Lahuerta, MD, PhD, of Hospital 12 de Octubre in Madrid, Spain, and colleagues reported the results in the Journal of Clinical Oncology.

Of the 609 patients, 286 (47%) achieved CR and had a significantly longer PFS (median, 49 months) than those who achieved nCR (median, 37 months), PR (median, 34 months) or less than PR (median, 11 months).

Patients who achieved CR also had a significantly longer OS (median, 128 months) than those who achieved PR (median, 75 months) or less than PR (median, 28 months), but not nCR (median, 77 months).

But patients who achieved CR and were still MRD-positive had a similar PFS (median, 27 months) to those patients who achieved nCR and PR and were MRD-positive (median 27 and 29 months, respectively). Median OS for MRD-positive patients in CR was a median 59 months, compared to 64 and 65 months, respectively, for MRD-positive patients in nCR and PR.

The team found that only MRD negativity significantly prolonged PFS and OS. Patients who were MRD-negative, even without achieving a CR, had a median PFS of 63 months (P<0.001) and the median OS not reached (P<0.001).

According to their paper, the investigators consider MRD negativity to be “one of the most relevant clinical end points and an aim of MM treatment of transplant-eligible and elderly patients who can tolerate intensive therapies.”

The team also investigated whether MRD negativity could be used as a meaningful clinical endpoint. They compared outcomes between patients who achieved CR according to MRD status before and after high-dose therapy and autologous stem cell transplant (ASCT).

Patients who were MRD-positive before transplant but MRD-negative afterwards had similar PFS and OS compared to patients who were MRD-negative before and after transplant. Patients who remained MRD-positive after transplant had inferior PFS and OS.

The team believes these results “support the adoption of MRD testing in routine practice to help discriminate between patients with clinically meaningful (MRD-negative) and misleading (MRD- positive) CRs.”

They noted, however, that a limitation of the study was the use of 2 different flow cytometries (8- and 4-color) with different sensitivities (10^-5 and 10^-4, respectively).

They also cautioned that these results should not be used to tailor treatments. Rather, new clinical trials that incorporate MRD assessments at additional time points need to be conducted.

multiple myeloma

A team of researchers has confirmed that minimal residual disease (MRD) negativity is superior to complete response (CR) as a prognostic marker for progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma (MM).

MRD-positive patients who achieved CR had a similar survival to MRD-positive patients who achieved near CR (nCR) or partial response (PR). And this held true despite different induction regimens, disease stages, patient ages, cytogenetic groups, and whether the patients were transplant eligible or ineligible.

The team conducted the pooled analysis on behalf of the GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group.

They analyzed data from a large pool of 609 patients newly diagnosed with MM enrolled in 3 clinical trials—GEM 2000 (n=256), GEM2005MENOS65 (n=226), and GEM2010MAS65 (n=127). All patients had MRD assessments 9 months after study enrollment. The median follow-up was 71 months.

Juan-Jose Lahuerta, MD, PhD, of Hospital 12 de Octubre in Madrid, Spain, and colleagues reported the results in the Journal of Clinical Oncology.

Of the 609 patients, 286 (47%) achieved CR and had a significantly longer PFS (median, 49 months) than those who achieved nCR (median, 37 months), PR (median, 34 months) or less than PR (median, 11 months).

Patients who achieved CR also had a significantly longer OS (median, 128 months) than those who achieved PR (median, 75 months) or less than PR (median, 28 months), but not nCR (median, 77 months).

But patients who achieved CR and were still MRD-positive had a similar PFS (median, 27 months) to those patients who achieved nCR and PR and were MRD-positive (median 27 and 29 months, respectively). Median OS for MRD-positive patients in CR was a median 59 months, compared to 64 and 65 months, respectively, for MRD-positive patients in nCR and PR.

The team found that only MRD negativity significantly prolonged PFS and OS. Patients who were MRD-negative, even without achieving a CR, had a median PFS of 63 months (P<0.001) and the median OS not reached (P<0.001).

According to their paper, the investigators consider MRD negativity to be “one of the most relevant clinical end points and an aim of MM treatment of transplant-eligible and elderly patients who can tolerate intensive therapies.”

The team also investigated whether MRD negativity could be used as a meaningful clinical endpoint. They compared outcomes between patients who achieved CR according to MRD status before and after high-dose therapy and autologous stem cell transplant (ASCT).

Patients who were MRD-positive before transplant but MRD-negative afterwards had similar PFS and OS compared to patients who were MRD-negative before and after transplant. Patients who remained MRD-positive after transplant had inferior PFS and OS.

The team believes these results “support the adoption of MRD testing in routine practice to help discriminate between patients with clinically meaningful (MRD-negative) and misleading (MRD- positive) CRs.”

They noted, however, that a limitation of the study was the use of 2 different flow cytometries (8- and 4-color) with different sensitivities (10^-5 and 10^-4, respectively).

They also cautioned that these results should not be used to tailor treatments. Rather, new clinical trials that incorporate MRD assessments at additional time points need to be conducted.

multiple myeloma

A team of researchers has confirmed that minimal residual disease (MRD) negativity is superior to complete response (CR) as a prognostic marker for progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma (MM).

MRD-positive patients who achieved CR had a similar survival to MRD-positive patients who achieved near CR (nCR) or partial response (PR). And this held true despite different induction regimens, disease stages, patient ages, cytogenetic groups, and whether the patients were transplant eligible or ineligible.

The team conducted the pooled analysis on behalf of the GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group.

They analyzed data from a large pool of 609 patients newly diagnosed with MM enrolled in 3 clinical trials—GEM 2000 (n=256), GEM2005MENOS65 (n=226), and GEM2010MAS65 (n=127). All patients had MRD assessments 9 months after study enrollment. The median follow-up was 71 months.

Juan-Jose Lahuerta, MD, PhD, of Hospital 12 de Octubre in Madrid, Spain, and colleagues reported the results in the Journal of Clinical Oncology.

Of the 609 patients, 286 (47%) achieved CR and had a significantly longer PFS (median, 49 months) than those who achieved nCR (median, 37 months), PR (median, 34 months) or less than PR (median, 11 months).

Patients who achieved CR also had a significantly longer OS (median, 128 months) than those who achieved PR (median, 75 months) or less than PR (median, 28 months), but not nCR (median, 77 months).

But patients who achieved CR and were still MRD-positive had a similar PFS (median, 27 months) to those patients who achieved nCR and PR and were MRD-positive (median 27 and 29 months, respectively). Median OS for MRD-positive patients in CR was a median 59 months, compared to 64 and 65 months, respectively, for MRD-positive patients in nCR and PR.

The team found that only MRD negativity significantly prolonged PFS and OS. Patients who were MRD-negative, even without achieving a CR, had a median PFS of 63 months (P<0.001) and the median OS not reached (P<0.001).

According to their paper, the investigators consider MRD negativity to be “one of the most relevant clinical end points and an aim of MM treatment of transplant-eligible and elderly patients who can tolerate intensive therapies.”

The team also investigated whether MRD negativity could be used as a meaningful clinical endpoint. They compared outcomes between patients who achieved CR according to MRD status before and after high-dose therapy and autologous stem cell transplant (ASCT).

Patients who were MRD-positive before transplant but MRD-negative afterwards had similar PFS and OS compared to patients who were MRD-negative before and after transplant. Patients who remained MRD-positive after transplant had inferior PFS and OS.

The team believes these results “support the adoption of MRD testing in routine practice to help discriminate between patients with clinically meaningful (MRD-negative) and misleading (MRD- positive) CRs.”

They noted, however, that a limitation of the study was the use of 2 different flow cytometries (8- and 4-color) with different sensitivities (10^-5 and 10^-4, respectively).

They also cautioned that these results should not be used to tailor treatments. Rather, new clinical trials that incorporate MRD assessments at additional time points need to be conducted.

Photo credit: American Chemical Society

A new compound combining the antimalarial drug artemisinin and luminol could help crime scene technicians detect blood spots with fewer false identifications.

Luminol, which is often combined with hydrogen peroxide, reacts with the heme groups in blood, producing a bright blue glow, known as chemiluminescence.

However, luminol is subject to false positives due to interference from biomolecules and metal ions, and from the breakdown products of hydrogen peroxide.

Artemisinin is a natural peroxide that is more stable than hydrogen peroxide in the presence of common ions and more resistant to interference.

So investigators decided to combine artemisinin with luminol in an effort to minimize erroneous bloodstain identifications. They showed that the luminol-artemisinin combination is more selective than luminol-hydrogen peroxide.

They challenged the new combination with components of bleaches and disinfectants, which criminals often use to clean up a crime scene. The new compound could distinguish blood from coffee, tea, and brown sugar stains.

The investigators also successfully tested the new luminol-artemisinin compound using a smartphone to obtain results. This new method could provide highly accurate, cost-effective, on-scene analyses.

They believe the favorable sensitivity and selectivity of this method makes it promising in forensic pursuits.

Guobao Xu, PhD, of the Chinese Academy of Sciences in Beijing, People’s Republic of China, and colleagues reported these findings in the American Chemical Society’s journal, Analytical Chemistry.

The authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Chinese Academy of Science President's International Fellowship Initiative Project, and the Chinese Academy of Sciences-the Academy of Sciences for the Developing World President's Fellowship Programme. 

Photo credit: American Chemical Society

A new compound combining the antimalarial drug artemisinin and luminol could help crime scene technicians detect blood spots with fewer false identifications.

Luminol, which is often combined with hydrogen peroxide, reacts with the heme groups in blood, producing a bright blue glow, known as chemiluminescence.

However, luminol is subject to false positives due to interference from biomolecules and metal ions, and from the breakdown products of hydrogen peroxide.

Artemisinin is a natural peroxide that is more stable than hydrogen peroxide in the presence of common ions and more resistant to interference.

So investigators decided to combine artemisinin with luminol in an effort to minimize erroneous bloodstain identifications. They showed that the luminol-artemisinin combination is more selective than luminol-hydrogen peroxide.

They challenged the new combination with components of bleaches and disinfectants, which criminals often use to clean up a crime scene. The new compound could distinguish blood from coffee, tea, and brown sugar stains.

The investigators also successfully tested the new luminol-artemisinin compound using a smartphone to obtain results. This new method could provide highly accurate, cost-effective, on-scene analyses.

They believe the favorable sensitivity and selectivity of this method makes it promising in forensic pursuits.

Guobao Xu, PhD, of the Chinese Academy of Sciences in Beijing, People’s Republic of China, and colleagues reported these findings in the American Chemical Society’s journal, Analytical Chemistry.

The authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Chinese Academy of Science President's International Fellowship Initiative Project, and the Chinese Academy of Sciences-the Academy of Sciences for the Developing World President's Fellowship Programme. 

Photo credit: American Chemical Society

A new compound combining the antimalarial drug artemisinin and luminol could help crime scene technicians detect blood spots with fewer false identifications.

Luminol, which is often combined with hydrogen peroxide, reacts with the heme groups in blood, producing a bright blue glow, known as chemiluminescence.

However, luminol is subject to false positives due to interference from biomolecules and metal ions, and from the breakdown products of hydrogen peroxide.

Artemisinin is a natural peroxide that is more stable than hydrogen peroxide in the presence of common ions and more resistant to interference.

So investigators decided to combine artemisinin with luminol in an effort to minimize erroneous bloodstain identifications. They showed that the luminol-artemisinin combination is more selective than luminol-hydrogen peroxide.

They challenged the new combination with components of bleaches and disinfectants, which criminals often use to clean up a crime scene. The new compound could distinguish blood from coffee, tea, and brown sugar stains.

The investigators also successfully tested the new luminol-artemisinin compound using a smartphone to obtain results. This new method could provide highly accurate, cost-effective, on-scene analyses.

They believe the favorable sensitivity and selectivity of this method makes it promising in forensic pursuits.

Guobao Xu, PhD, of the Chinese Academy of Sciences in Beijing, People’s Republic of China, and colleagues reported these findings in the American Chemical Society’s journal, Analytical Chemistry.

The authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Chinese Academy of Science President's International Fellowship Initiative Project, and the Chinese Academy of Sciences-the Academy of Sciences for the Developing World President's Fellowship Programme. 

IN THIS ARTICLE

• Diagnosis
• Treatment/management
• Physcial signs suggestive of CVID in patients with appropriate history
• Case outcome

A 60-year-old woman with a recent history of air and cruise ship travel presented with symptoms consistent with acute sinusitis. She had a 34–pack-year history of cigarette smoking but had quit at age 50. Her medical history was significant for hypothyroidism, hypertension, coronary artery disease, mild asthma, and COPD. Past surgical history included coronary artery bypass, abdominal hysterectomy, and cholecystectomy. Her medications included inhaled bronchodilators, thyroxin, hydrochlorothiazide, nitrates, ß-blockers, and calcium channel blockers.

Over the next five years, she presented with frequent episodes of respiratory illness for which she received multiple courses of antibiotics, inhaled bronchodilators, and oral as well as inhaled corticosteroids. She consequently became increasingly sensitized to multiple antibiotic classes and was frequently hospitalized for the treatment of her respiratory illnesses.

Common variable immunodeficiency disorders (collectively known as CVID) are the most common clinically significant immunodeficiency diseases among adults.¹ Manifesting clinically as frequent, unusually severe or recalcitrant bacterial infections of the ear, sinus, respiratory tree, and/or gastrointestinal tract, CVID is genetically induced.² Additionally, these disorders can predispose individuals to autoimmune conditions and to cancers involving B lymphocytes.³ Often thought to be a disease of younger people, CVID can occur across the age span.⁴

The immune dysfunction that characterizes CVID is believed to result from underlying genetic defects that affect the differentiation of B cells, leading to faulty immunoglobulin (Ig) synthesis. Recent advances that allow the detection of multiple novel susceptibility loci for CVID have dramatically increased our understanding of the pathophysiology and pathogenesis of this disorder.⁵ These advances are being used to refine the diagnostic parameters of CVID and in the future may help clinicians tailor treatment protocols to specific genetic defects.^5,6

Although considered rare, CVID is often unrecognized; the incidence is likely much higher than the current estimates of 1:10,000 to 1:50,000.⁷ About 13% to 23% of individuals with chronic sinusitis are thought to be affected by CVID.⁸ While it is most commonly diagnosed during the second and third decades of life, it can be diagnosed at any time during the lifespan.⁴ A high burden of disease is associated with this disorder, as hospitalizations and costly, aggressive treatment regimens are needed to manage the resultant bacterial infections and sequelae.²

Increased awareness of CVID among primary care providers is needed to assure prompt diagnosis and to avoid unnecessary complications associated with delayed treatment. The diagnostic workup is complex, and referral to immunology for specific diagnosis and treatment is strongly advised. Recognition is the first step, and primary care providers must include primary immunodeficiency disorders, including CVID, in their differential to avert a missed diagnosis and to ensure optimal treatment.⁹

CLINICAL MANIFESTATIONS/PATIENT HISTORY

Frequent and severe infections are a hallmark of CVID. The most common types of infections seen in CVID are sinusitis, conjunctivitis, otitis media, bronchitis, pneumonia, and gastroenteritis.¹⁰ These primary bacterial infections can disseminate, causing septicemia and/or central nervous system infection.¹¹ The usual infectious pathogens are encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae, but atypical infections due to organisms such as Pneumocystis carinii and Mycoplasma pneumoniae also occur in some patients.^12,13

Although the majority of CVID cases occur sporadically, family history is helpful in securing the correct diagnosis.¹⁵ Known immunodeficiency, unusual susceptibility to infections, autoimmune diseases, hematologic malignancy, or death caused by infection in other family members should increase the provider’s index of suspicion for CVID.¹⁶

Many genetic defects have been implicated in CVID, yet the wide phenotypic expression found even in persons with similar genetic profiles implies that CVID has a complex genetic transmission pattern.¹⁵ Known or suspected consanguinity in parents or grandparents increases the risk for CVID.⁶

Although these family history elements occur infrequently, they increase the likelihood of severe opportunistic infection, which can cause organ damage or even death.^1,17 Being alert for these elements of family history can help to avoid delays in diagnosis and treatment and eventual organ damage.²

DIFFERENTIAL DIAGNOSIS

When considering the differential diagnosis for the primary features of CVID, other etiologies that should be considered include allergies, environmental exposures, uncontrolled gastroesophageal reflux disease, structural abnormalities of the upper respiratory tract, and celiac disease.^5,10,18,19 Far less common but still worthy of consideration are other genetic conditions, such as primary ciliary dyskinesia, cystic fibrosis, thymic dysfunction or carcinoma, and protein-losing enteropathies.^20,21

A number of conditions can cause immunosuppression. Transient reductions in serum Ig levels can occur in the presence of serious infections.²² Long-term, high-dose use of some medications, such as corticosteroids, or use of anticonvulsants may reduce antibody availability. Chronic illnesses, malignancy, and malnutrition can also play a role in immunosuppression.¹⁹ CVID shares features with a large number of primary immune diseases, and these as well as other causes of hypogammaglobulinemia must be excluded before the diagnosis of CVID can be made.¹

DIAGNOSIS

While infectious disease is a common reason patients seek medical care, few patients presenting with one will have CVID. Nevertheless, immunologic evaluations should be performed and appropriate referral to an immunology specialist is strongly recommended when more than one severe infection arises in a year’s time; when a pattern of severe or unusual infections presents over a period of time; when bronchiectasis is present; or when infections do not resolve with conventional treatment.¹⁶ In addition, the physical findings noted in the Table, when combined with a history of recurrent infections, autoimmune disorders, or lymphocytic malignancy, should prompt evaluation for CVID.^10,16,18,23

The diagnosis of CVID requires testing for low serum levels of total IgG, IgG subclasses, IgA, and IgM. In CVID, IgG and IgA levels will be reduced, and occasionally IgM levels will also be diminished.²⁴ Unless an active infection is present, there will be no change in the patient’s routine blood tests, such as the complete blood count and total complement levels.

The diagnosis is also based on demonstration of a deficient antibody response to protein (tetanus) and polysaccharide (pneumonia) vaccine antigens.²¹ A minimal reaction to these vaccines should prompt referral to an immunology specialist for additional testing and a plan of care.²⁵ However, whenever the index of suspicion for CVID is high, prompt referral to immunology should not be delayed to perform further testing.¹⁶

TREATMENT/MANAGEMENT

IgG replacement therapy, which treats the underlying pathophysiology of CVID by supplementing one of the deficient antibodies, is the standard treatment for CVID. IgG is considered a blood product since it is made from human plasma. Patients may experience untoward reactions to IgG replacement therapy, similar to transfusion reactions; such reactions commonly include back pain, low-grade fever, muscle and joint discomfort, and fatigue. These unpleasant effects can be minimized with the prophylactic use of antihistamines, antipyretics, or even glucocorticoids.²⁶

Although IgG replacement therapy has high upfront costs, it increases patients’ well-being considerably by preventing multiple or recurrent infections and the resultant hospitalizations for antibiotic therapy.²⁷ Home infusion of IgG can minimize costs as well as increase patient autonomy.²⁸ With home infusions, IgG is administered via a multisite subcutaneous route using a slow-infusion mechanical pump. Subcutaneous infusions generally take four to six hours, depending on the number of sites used. Some patients can infuse while they sleep, which increases patient satisfaction with the treatment.²⁷

Infections in persons with CVID can be severe and may lead to organ-system compromise, requiring aggressive therapy aimed at supporting the function of the affected organ systems. For example, patients with CVID can develop unrelenting vomiting and diarrhea, which may require inpatient admission for rehydration and stabilization until the infection can be treated adequately.³²

Treatment options remain limited for the subset of CVID patients who develop severe complications, such as interstitial lung disease or neoplasms. These complications are associated with a significant increase in patient mortality, and allogeneic hematopoietic stem cell transplantation may be indicated for patients who develop them. This potentially curative treatment is being explored in ongoing research trials.³³

PATIENT EDUCATION

Scrupulous hand hygiene, careful avoidance of infectious exposures, watchful food handling and preparation, and lifestyle choices that support good general health are key elements of self-care for patients who have CVID. Preventive measures serve this population well by helping to reduce some of the complications of this serious disease.

Patients with CVID should understand keys aspects regarding its diagnosis, treatment, and prognosis. Specifically, they should know that people who have CVID are born missing some of the body’s immune defenses, which increases their risk for infection, especially of the sinuses, lungs, and gut. Sometimes it takes years to make this diagnosis, because it is a rare cause of common symptoms.

The patient was referred to immunology, and a diagnosis of CVID was made. She was successfully treated with subcutaneous IgG replacement therapy. She died due to overwhelming sepsis after an episode of pneumonia at age 84.

CONCLUSION

The secret to prompt detection of CVID is adding it to the differential diagnosis of recurrent infections. Timely recognition and appropriate referral prevent serious complications, since successful treatment options are available.

Special thanks to Doug Bartelt, DNP, APNP, NP-C.

IN THIS ARTICLE

• Diagnosis
• Treatment/management
• Physcial signs suggestive of CVID in patients with appropriate history
• Case outcome

A 60-year-old woman with a recent history of air and cruise ship travel presented with symptoms consistent with acute sinusitis. She had a 34–pack-year history of cigarette smoking but had quit at age 50. Her medical history was significant for hypothyroidism, hypertension, coronary artery disease, mild asthma, and COPD. Past surgical history included coronary artery bypass, abdominal hysterectomy, and cholecystectomy. Her medications included inhaled bronchodilators, thyroxin, hydrochlorothiazide, nitrates, ß-blockers, and calcium channel blockers.

Over the next five years, she presented with frequent episodes of respiratory illness for which she received multiple courses of antibiotics, inhaled bronchodilators, and oral as well as inhaled corticosteroids. She consequently became increasingly sensitized to multiple antibiotic classes and was frequently hospitalized for the treatment of her respiratory illnesses.

Common variable immunodeficiency disorders (collectively known as CVID) are the most common clinically significant immunodeficiency diseases among adults.¹ Manifesting clinically as frequent, unusually severe or recalcitrant bacterial infections of the ear, sinus, respiratory tree, and/or gastrointestinal tract, CVID is genetically induced.² Additionally, these disorders can predispose individuals to autoimmune conditions and to cancers involving B lymphocytes.³ Often thought to be a disease of younger people, CVID can occur across the age span.⁴

The immune dysfunction that characterizes CVID is believed to result from underlying genetic defects that affect the differentiation of B cells, leading to faulty immunoglobulin (Ig) synthesis. Recent advances that allow the detection of multiple novel susceptibility loci for CVID have dramatically increased our understanding of the pathophysiology and pathogenesis of this disorder.⁵ These advances are being used to refine the diagnostic parameters of CVID and in the future may help clinicians tailor treatment protocols to specific genetic defects.^5,6

Although considered rare, CVID is often unrecognized; the incidence is likely much higher than the current estimates of 1:10,000 to 1:50,000.⁷ About 13% to 23% of individuals with chronic sinusitis are thought to be affected by CVID.⁸ While it is most commonly diagnosed during the second and third decades of life, it can be diagnosed at any time during the lifespan.⁴ A high burden of disease is associated with this disorder, as hospitalizations and costly, aggressive treatment regimens are needed to manage the resultant bacterial infections and sequelae.²

Increased awareness of CVID among primary care providers is needed to assure prompt diagnosis and to avoid unnecessary complications associated with delayed treatment. The diagnostic workup is complex, and referral to immunology for specific diagnosis and treatment is strongly advised. Recognition is the first step, and primary care providers must include primary immunodeficiency disorders, including CVID, in their differential to avert a missed diagnosis and to ensure optimal treatment.⁹

CLINICAL MANIFESTATIONS/PATIENT HISTORY

Frequent and severe infections are a hallmark of CVID. The most common types of infections seen in CVID are sinusitis, conjunctivitis, otitis media, bronchitis, pneumonia, and gastroenteritis.¹⁰ These primary bacterial infections can disseminate, causing septicemia and/or central nervous system infection.¹¹ The usual infectious pathogens are encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae, but atypical infections due to organisms such as Pneumocystis carinii and Mycoplasma pneumoniae also occur in some patients.^12,13

Although the majority of CVID cases occur sporadically, family history is helpful in securing the correct diagnosis.¹⁵ Known immunodeficiency, unusual susceptibility to infections, autoimmune diseases, hematologic malignancy, or death caused by infection in other family members should increase the provider’s index of suspicion for CVID.¹⁶

Many genetic defects have been implicated in CVID, yet the wide phenotypic expression found even in persons with similar genetic profiles implies that CVID has a complex genetic transmission pattern.¹⁵ Known or suspected consanguinity in parents or grandparents increases the risk for CVID.⁶

Although these family history elements occur infrequently, they increase the likelihood of severe opportunistic infection, which can cause organ damage or even death.^1,17 Being alert for these elements of family history can help to avoid delays in diagnosis and treatment and eventual organ damage.²

DIFFERENTIAL DIAGNOSIS

When considering the differential diagnosis for the primary features of CVID, other etiologies that should be considered include allergies, environmental exposures, uncontrolled gastroesophageal reflux disease, structural abnormalities of the upper respiratory tract, and celiac disease.^5,10,18,19 Far less common but still worthy of consideration are other genetic conditions, such as primary ciliary dyskinesia, cystic fibrosis, thymic dysfunction or carcinoma, and protein-losing enteropathies.^20,21

A number of conditions can cause immunosuppression. Transient reductions in serum Ig levels can occur in the presence of serious infections.²² Long-term, high-dose use of some medications, such as corticosteroids, or use of anticonvulsants may reduce antibody availability. Chronic illnesses, malignancy, and malnutrition can also play a role in immunosuppression.¹⁹ CVID shares features with a large number of primary immune diseases, and these as well as other causes of hypogammaglobulinemia must be excluded before the diagnosis of CVID can be made.¹

DIAGNOSIS

While infectious disease is a common reason patients seek medical care, few patients presenting with one will have CVID. Nevertheless, immunologic evaluations should be performed and appropriate referral to an immunology specialist is strongly recommended when more than one severe infection arises in a year’s time; when a pattern of severe or unusual infections presents over a period of time; when bronchiectasis is present; or when infections do not resolve with conventional treatment.¹⁶ In addition, the physical findings noted in the Table, when combined with a history of recurrent infections, autoimmune disorders, or lymphocytic malignancy, should prompt evaluation for CVID.^10,16,18,23

The diagnosis of CVID requires testing for low serum levels of total IgG, IgG subclasses, IgA, and IgM. In CVID, IgG and IgA levels will be reduced, and occasionally IgM levels will also be diminished.²⁴ Unless an active infection is present, there will be no change in the patient’s routine blood tests, such as the complete blood count and total complement levels.

The diagnosis is also based on demonstration of a deficient antibody response to protein (tetanus) and polysaccharide (pneumonia) vaccine antigens.²¹ A minimal reaction to these vaccines should prompt referral to an immunology specialist for additional testing and a plan of care.²⁵ However, whenever the index of suspicion for CVID is high, prompt referral to immunology should not be delayed to perform further testing.¹⁶

TREATMENT/MANAGEMENT

IgG replacement therapy, which treats the underlying pathophysiology of CVID by supplementing one of the deficient antibodies, is the standard treatment for CVID. IgG is considered a blood product since it is made from human plasma. Patients may experience untoward reactions to IgG replacement therapy, similar to transfusion reactions; such reactions commonly include back pain, low-grade fever, muscle and joint discomfort, and fatigue. These unpleasant effects can be minimized with the prophylactic use of antihistamines, antipyretics, or even glucocorticoids.²⁶

Although IgG replacement therapy has high upfront costs, it increases patients’ well-being considerably by preventing multiple or recurrent infections and the resultant hospitalizations for antibiotic therapy.²⁷ Home infusion of IgG can minimize costs as well as increase patient autonomy.²⁸ With home infusions, IgG is administered via a multisite subcutaneous route using a slow-infusion mechanical pump. Subcutaneous infusions generally take four to six hours, depending on the number of sites used. Some patients can infuse while they sleep, which increases patient satisfaction with the treatment.²⁷

Infections in persons with CVID can be severe and may lead to organ-system compromise, requiring aggressive therapy aimed at supporting the function of the affected organ systems. For example, patients with CVID can develop unrelenting vomiting and diarrhea, which may require inpatient admission for rehydration and stabilization until the infection can be treated adequately.³²

Treatment options remain limited for the subset of CVID patients who develop severe complications, such as interstitial lung disease or neoplasms. These complications are associated with a significant increase in patient mortality, and allogeneic hematopoietic stem cell transplantation may be indicated for patients who develop them. This potentially curative treatment is being explored in ongoing research trials.³³

PATIENT EDUCATION

Scrupulous hand hygiene, careful avoidance of infectious exposures, watchful food handling and preparation, and lifestyle choices that support good general health are key elements of self-care for patients who have CVID. Preventive measures serve this population well by helping to reduce some of the complications of this serious disease.

Patients with CVID should understand keys aspects regarding its diagnosis, treatment, and prognosis. Specifically, they should know that people who have CVID are born missing some of the body’s immune defenses, which increases their risk for infection, especially of the sinuses, lungs, and gut. Sometimes it takes years to make this diagnosis, because it is a rare cause of common symptoms.

The patient was referred to immunology, and a diagnosis of CVID was made. She was successfully treated with subcutaneous IgG replacement therapy. She died due to overwhelming sepsis after an episode of pneumonia at age 84.

CONCLUSION

The secret to prompt detection of CVID is adding it to the differential diagnosis of recurrent infections. Timely recognition and appropriate referral prevent serious complications, since successful treatment options are available.

Special thanks to Doug Bartelt, DNP, APNP, NP-C.

IN THIS ARTICLE

• Diagnosis
• Treatment/management
• Physcial signs suggestive of CVID in patients with appropriate history
• Case outcome

A 60-year-old woman with a recent history of air and cruise ship travel presented with symptoms consistent with acute sinusitis. She had a 34–pack-year history of cigarette smoking but had quit at age 50. Her medical history was significant for hypothyroidism, hypertension, coronary artery disease, mild asthma, and COPD. Past surgical history included coronary artery bypass, abdominal hysterectomy, and cholecystectomy. Her medications included inhaled bronchodilators, thyroxin, hydrochlorothiazide, nitrates, ß-blockers, and calcium channel blockers.

Over the next five years, she presented with frequent episodes of respiratory illness for which she received multiple courses of antibiotics, inhaled bronchodilators, and oral as well as inhaled corticosteroids. She consequently became increasingly sensitized to multiple antibiotic classes and was frequently hospitalized for the treatment of her respiratory illnesses.

Common variable immunodeficiency disorders (collectively known as CVID) are the most common clinically significant immunodeficiency diseases among adults.¹ Manifesting clinically as frequent, unusually severe or recalcitrant bacterial infections of the ear, sinus, respiratory tree, and/or gastrointestinal tract, CVID is genetically induced.² Additionally, these disorders can predispose individuals to autoimmune conditions and to cancers involving B lymphocytes.³ Often thought to be a disease of younger people, CVID can occur across the age span.⁴

The immune dysfunction that characterizes CVID is believed to result from underlying genetic defects that affect the differentiation of B cells, leading to faulty immunoglobulin (Ig) synthesis. Recent advances that allow the detection of multiple novel susceptibility loci for CVID have dramatically increased our understanding of the pathophysiology and pathogenesis of this disorder.⁵ These advances are being used to refine the diagnostic parameters of CVID and in the future may help clinicians tailor treatment protocols to specific genetic defects.^5,6

Although considered rare, CVID is often unrecognized; the incidence is likely much higher than the current estimates of 1:10,000 to 1:50,000.⁷ About 13% to 23% of individuals with chronic sinusitis are thought to be affected by CVID.⁸ While it is most commonly diagnosed during the second and third decades of life, it can be diagnosed at any time during the lifespan.⁴ A high burden of disease is associated with this disorder, as hospitalizations and costly, aggressive treatment regimens are needed to manage the resultant bacterial infections and sequelae.²

Increased awareness of CVID among primary care providers is needed to assure prompt diagnosis and to avoid unnecessary complications associated with delayed treatment. The diagnostic workup is complex, and referral to immunology for specific diagnosis and treatment is strongly advised. Recognition is the first step, and primary care providers must include primary immunodeficiency disorders, including CVID, in their differential to avert a missed diagnosis and to ensure optimal treatment.⁹

CLINICAL MANIFESTATIONS/PATIENT HISTORY

Frequent and severe infections are a hallmark of CVID. The most common types of infections seen in CVID are sinusitis, conjunctivitis, otitis media, bronchitis, pneumonia, and gastroenteritis.¹⁰ These primary bacterial infections can disseminate, causing septicemia and/or central nervous system infection.¹¹ The usual infectious pathogens are encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae, but atypical infections due to organisms such as Pneumocystis carinii and Mycoplasma pneumoniae also occur in some patients.^12,13

Although the majority of CVID cases occur sporadically, family history is helpful in securing the correct diagnosis.¹⁵ Known immunodeficiency, unusual susceptibility to infections, autoimmune diseases, hematologic malignancy, or death caused by infection in other family members should increase the provider’s index of suspicion for CVID.¹⁶

Many genetic defects have been implicated in CVID, yet the wide phenotypic expression found even in persons with similar genetic profiles implies that CVID has a complex genetic transmission pattern.¹⁵ Known or suspected consanguinity in parents or grandparents increases the risk for CVID.⁶

Although these family history elements occur infrequently, they increase the likelihood of severe opportunistic infection, which can cause organ damage or even death.^1,17 Being alert for these elements of family history can help to avoid delays in diagnosis and treatment and eventual organ damage.²

DIFFERENTIAL DIAGNOSIS

When considering the differential diagnosis for the primary features of CVID, other etiologies that should be considered include allergies, environmental exposures, uncontrolled gastroesophageal reflux disease, structural abnormalities of the upper respiratory tract, and celiac disease.^5,10,18,19 Far less common but still worthy of consideration are other genetic conditions, such as primary ciliary dyskinesia, cystic fibrosis, thymic dysfunction or carcinoma, and protein-losing enteropathies.^20,21

A number of conditions can cause immunosuppression. Transient reductions in serum Ig levels can occur in the presence of serious infections.²² Long-term, high-dose use of some medications, such as corticosteroids, or use of anticonvulsants may reduce antibody availability. Chronic illnesses, malignancy, and malnutrition can also play a role in immunosuppression.¹⁹ CVID shares features with a large number of primary immune diseases, and these as well as other causes of hypogammaglobulinemia must be excluded before the diagnosis of CVID can be made.¹

DIAGNOSIS

While infectious disease is a common reason patients seek medical care, few patients presenting with one will have CVID. Nevertheless, immunologic evaluations should be performed and appropriate referral to an immunology specialist is strongly recommended when more than one severe infection arises in a year’s time; when a pattern of severe or unusual infections presents over a period of time; when bronchiectasis is present; or when infections do not resolve with conventional treatment.¹⁶ In addition, the physical findings noted in the Table, when combined with a history of recurrent infections, autoimmune disorders, or lymphocytic malignancy, should prompt evaluation for CVID.^10,16,18,23

The diagnosis of CVID requires testing for low serum levels of total IgG, IgG subclasses, IgA, and IgM. In CVID, IgG and IgA levels will be reduced, and occasionally IgM levels will also be diminished.²⁴ Unless an active infection is present, there will be no change in the patient’s routine blood tests, such as the complete blood count and total complement levels.

The diagnosis is also based on demonstration of a deficient antibody response to protein (tetanus) and polysaccharide (pneumonia) vaccine antigens.²¹ A minimal reaction to these vaccines should prompt referral to an immunology specialist for additional testing and a plan of care.²⁵ However, whenever the index of suspicion for CVID is high, prompt referral to immunology should not be delayed to perform further testing.¹⁶

TREATMENT/MANAGEMENT

IgG replacement therapy, which treats the underlying pathophysiology of CVID by supplementing one of the deficient antibodies, is the standard treatment for CVID. IgG is considered a blood product since it is made from human plasma. Patients may experience untoward reactions to IgG replacement therapy, similar to transfusion reactions; such reactions commonly include back pain, low-grade fever, muscle and joint discomfort, and fatigue. These unpleasant effects can be minimized with the prophylactic use of antihistamines, antipyretics, or even glucocorticoids.²⁶

Although IgG replacement therapy has high upfront costs, it increases patients’ well-being considerably by preventing multiple or recurrent infections and the resultant hospitalizations for antibiotic therapy.²⁷ Home infusion of IgG can minimize costs as well as increase patient autonomy.²⁸ With home infusions, IgG is administered via a multisite subcutaneous route using a slow-infusion mechanical pump. Subcutaneous infusions generally take four to six hours, depending on the number of sites used. Some patients can infuse while they sleep, which increases patient satisfaction with the treatment.²⁷

Infections in persons with CVID can be severe and may lead to organ-system compromise, requiring aggressive therapy aimed at supporting the function of the affected organ systems. For example, patients with CVID can develop unrelenting vomiting and diarrhea, which may require inpatient admission for rehydration and stabilization until the infection can be treated adequately.³²

Treatment options remain limited for the subset of CVID patients who develop severe complications, such as interstitial lung disease or neoplasms. These complications are associated with a significant increase in patient mortality, and allogeneic hematopoietic stem cell transplantation may be indicated for patients who develop them. This potentially curative treatment is being explored in ongoing research trials.³³

PATIENT EDUCATION

Scrupulous hand hygiene, careful avoidance of infectious exposures, watchful food handling and preparation, and lifestyle choices that support good general health are key elements of self-care for patients who have CVID. Preventive measures serve this population well by helping to reduce some of the complications of this serious disease.

Patients with CVID should understand keys aspects regarding its diagnosis, treatment, and prognosis. Specifically, they should know that people who have CVID are born missing some of the body’s immune defenses, which increases their risk for infection, especially of the sinuses, lungs, and gut. Sometimes it takes years to make this diagnosis, because it is a rare cause of common symptoms.

The patient was referred to immunology, and a diagnosis of CVID was made. She was successfully treated with subcutaneous IgG replacement therapy. She died due to overwhelming sepsis after an episode of pneumonia at age 84.

CONCLUSION

The secret to prompt detection of CVID is adding it to the differential diagnosis of recurrent infections. Timely recognition and appropriate referral prevent serious complications, since successful treatment options are available.

Special thanks to Doug Bartelt, DNP, APNP, NP-C.

The Trump administration has drafted a plan that would allow more employers to opt out of offering no-cost contraception coverage to women based on religious or moral grounds, according to a leaked copy of the interim rule.

The proposed rule, first obtained by the media outlet Vox, would greatly expand the religious exemption under the Affordable Care Act for employers otherwise subject to the ACA’s contraception mandate. If approved, the rule would allow additional entities and employers that object to the mandate for religious or moral reasons to be exempt from providing coverage. The exception would apply to plans sponsored by objecting employers, whether or not they operate as a nonprofit, according to the leaked rule.

[email protected]

On Twitter @legal_med

The Trump administration has drafted a plan that would allow more employers to opt out of offering no-cost contraception coverage to women based on religious or moral grounds, according to a leaked copy of the interim rule.

The proposed rule, first obtained by the media outlet Vox, would greatly expand the religious exemption under the Affordable Care Act for employers otherwise subject to the ACA’s contraception mandate. If approved, the rule would allow additional entities and employers that object to the mandate for religious or moral reasons to be exempt from providing coverage. The exception would apply to plans sponsored by objecting employers, whether or not they operate as a nonprofit, according to the leaked rule.

[email protected]

On Twitter @legal_med

The Trump administration has drafted a plan that would allow more employers to opt out of offering no-cost contraception coverage to women based on religious or moral grounds, according to a leaked copy of the interim rule.

The proposed rule, first obtained by the media outlet Vox, would greatly expand the religious exemption under the Affordable Care Act for employers otherwise subject to the ACA’s contraception mandate. If approved, the rule would allow additional entities and employers that object to the mandate for religious or moral reasons to be exempt from providing coverage. The exception would apply to plans sponsored by objecting employers, whether or not they operate as a nonprofit, according to the leaked rule.

[email protected]

On Twitter @legal_med