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Erosive hand OA evades dual IL-1 blocker’s effects
MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.
The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.
The phase 2a, multicenter, randomized, double-blind, placebo-controlled study she reported followed on from a phase 1 trial showing that ABT-981 could dose-dependently reduce neutrophil counts and markers of joint inflammation in patients with knee OA. So it was perhaps natural to see if it could potentially have an effect in patients with erosive hand OA.
The aim of the phase 2a trial was to evaluate the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA. After screening and a 45-day washout period, patients with confirmed erosive hand OA were randomized to receive ABT-981 200 mg injected every 2 weeks or matching placebo.
The primary endpoint was the change in Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain from baseline to 16 weeks, but no significant difference was observed. The mean change in AUSCAN pain was –9.2 for the 64 ABT-981-treated patients and –10.7 for placebo-treated patients (P = .039).
“There were similar results with AUSCAN function and tender and swollen joint counts,” Dr. Kloppenburg said.
There were also no differences seen in radiographic or MRI endpoints, such as the number of erosive joints, Kellgren and Lawrence scores, joint-space narrowing, or the presence of osteophytes.
Nevertheless, there was evidence that ABT-981 was decreasing inflammatory markers, such as high-sensitivity C-reactive protein and neutrophils. IL-1 alpha and IL-1 beta were difficult to measure, but data suggested that IL-1 was being blocked.
Disappointing results with cytokine targeting
Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.
While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.
His general conclusion was that targeting cytokines in hand OA had been “disappointing” with “small effect in subgroup of clinically inflamed IP [interphalangeal] joints.”
Dr. Chevalier questioned: “Is hand OA a real OA?” There are features of the disease that imply it could be more of a ligamentous or enthesitis disease, or perhaps a subchondral bone disorder.
Is erosive hand OA even an inflammatory disease? he asked. Are TNF and IL-1 the right targets? Perhaps not, given the research presented by Dr. Kloppenburg and others, he suggested. Further research needs to look for surrogate markers and try to quantify the structural evolution of the disease, he proposed.
It is important to talk about negative studies and to not make excuses for why they might be negative, Tonia Vincent, PhD, observed during the discussion that followed Dr. Chevalier’s presentation.
“If you do proper, randomized, controlled studies in decent numbers and you don’t see effect sizes, and the only times when you see things are when they are open-label, they are not randomized, you’re looking at small numbers, it just goes to show easy it is to over interpret the results of those small studies,” said Dr. Vincent, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology in Oxford, England.
“My conclusion, from my own in vivo studies and from what you’ve [Dr. Chevalier] just said, is that these are the wrong targets. Just because we are rheumatologists does not mean to say everything is about cytokines,” she said.
AbbVie funded the study. Dr. Kloppenburg acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. Dr. Chevalier disclosed working as an advisor to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma. Dr. Vincent did not report her disclosures.
[email protected]
On Twitter @rheumnews1
MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.
The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.
The phase 2a, multicenter, randomized, double-blind, placebo-controlled study she reported followed on from a phase 1 trial showing that ABT-981 could dose-dependently reduce neutrophil counts and markers of joint inflammation in patients with knee OA. So it was perhaps natural to see if it could potentially have an effect in patients with erosive hand OA.
The aim of the phase 2a trial was to evaluate the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA. After screening and a 45-day washout period, patients with confirmed erosive hand OA were randomized to receive ABT-981 200 mg injected every 2 weeks or matching placebo.
The primary endpoint was the change in Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain from baseline to 16 weeks, but no significant difference was observed. The mean change in AUSCAN pain was –9.2 for the 64 ABT-981-treated patients and –10.7 for placebo-treated patients (P = .039).
“There were similar results with AUSCAN function and tender and swollen joint counts,” Dr. Kloppenburg said.
There were also no differences seen in radiographic or MRI endpoints, such as the number of erosive joints, Kellgren and Lawrence scores, joint-space narrowing, or the presence of osteophytes.
Nevertheless, there was evidence that ABT-981 was decreasing inflammatory markers, such as high-sensitivity C-reactive protein and neutrophils. IL-1 alpha and IL-1 beta were difficult to measure, but data suggested that IL-1 was being blocked.
Disappointing results with cytokine targeting
Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.
While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.
His general conclusion was that targeting cytokines in hand OA had been “disappointing” with “small effect in subgroup of clinically inflamed IP [interphalangeal] joints.”
Dr. Chevalier questioned: “Is hand OA a real OA?” There are features of the disease that imply it could be more of a ligamentous or enthesitis disease, or perhaps a subchondral bone disorder.
Is erosive hand OA even an inflammatory disease? he asked. Are TNF and IL-1 the right targets? Perhaps not, given the research presented by Dr. Kloppenburg and others, he suggested. Further research needs to look for surrogate markers and try to quantify the structural evolution of the disease, he proposed.
It is important to talk about negative studies and to not make excuses for why they might be negative, Tonia Vincent, PhD, observed during the discussion that followed Dr. Chevalier’s presentation.
“If you do proper, randomized, controlled studies in decent numbers and you don’t see effect sizes, and the only times when you see things are when they are open-label, they are not randomized, you’re looking at small numbers, it just goes to show easy it is to over interpret the results of those small studies,” said Dr. Vincent, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology in Oxford, England.
“My conclusion, from my own in vivo studies and from what you’ve [Dr. Chevalier] just said, is that these are the wrong targets. Just because we are rheumatologists does not mean to say everything is about cytokines,” she said.
AbbVie funded the study. Dr. Kloppenburg acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. Dr. Chevalier disclosed working as an advisor to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma. Dr. Vincent did not report her disclosures.
[email protected]
On Twitter @rheumnews1
MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.
The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.
The phase 2a, multicenter, randomized, double-blind, placebo-controlled study she reported followed on from a phase 1 trial showing that ABT-981 could dose-dependently reduce neutrophil counts and markers of joint inflammation in patients with knee OA. So it was perhaps natural to see if it could potentially have an effect in patients with erosive hand OA.
The aim of the phase 2a trial was to evaluate the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA. After screening and a 45-day washout period, patients with confirmed erosive hand OA were randomized to receive ABT-981 200 mg injected every 2 weeks or matching placebo.
The primary endpoint was the change in Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain from baseline to 16 weeks, but no significant difference was observed. The mean change in AUSCAN pain was –9.2 for the 64 ABT-981-treated patients and –10.7 for placebo-treated patients (P = .039).
“There were similar results with AUSCAN function and tender and swollen joint counts,” Dr. Kloppenburg said.
There were also no differences seen in radiographic or MRI endpoints, such as the number of erosive joints, Kellgren and Lawrence scores, joint-space narrowing, or the presence of osteophytes.
Nevertheless, there was evidence that ABT-981 was decreasing inflammatory markers, such as high-sensitivity C-reactive protein and neutrophils. IL-1 alpha and IL-1 beta were difficult to measure, but data suggested that IL-1 was being blocked.
Disappointing results with cytokine targeting
Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.
While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.
His general conclusion was that targeting cytokines in hand OA had been “disappointing” with “small effect in subgroup of clinically inflamed IP [interphalangeal] joints.”
Dr. Chevalier questioned: “Is hand OA a real OA?” There are features of the disease that imply it could be more of a ligamentous or enthesitis disease, or perhaps a subchondral bone disorder.
Is erosive hand OA even an inflammatory disease? he asked. Are TNF and IL-1 the right targets? Perhaps not, given the research presented by Dr. Kloppenburg and others, he suggested. Further research needs to look for surrogate markers and try to quantify the structural evolution of the disease, he proposed.
It is important to talk about negative studies and to not make excuses for why they might be negative, Tonia Vincent, PhD, observed during the discussion that followed Dr. Chevalier’s presentation.
“If you do proper, randomized, controlled studies in decent numbers and you don’t see effect sizes, and the only times when you see things are when they are open-label, they are not randomized, you’re looking at small numbers, it just goes to show easy it is to over interpret the results of those small studies,” said Dr. Vincent, professor of musculoskeletal biology at the Kennedy Institute of Rheumatology in Oxford, England.
“My conclusion, from my own in vivo studies and from what you’ve [Dr. Chevalier] just said, is that these are the wrong targets. Just because we are rheumatologists does not mean to say everything is about cytokines,” she said.
AbbVie funded the study. Dr. Kloppenburg acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. Dr. Chevalier disclosed working as an advisor to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma. Dr. Vincent did not report her disclosures.
[email protected]
On Twitter @rheumnews1
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The mean change in AUSCAN pain from baseline to week 16 was –9.2 and –10.7 comparing ABT-981 and placebo-treated patients (P = .039).
Data source: A phase 2a, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of ABT-981 in the treatment of 131 patients with erosive hand OA.
Disclosures: AbbVie funded the study. The study presenter acknowledged receiving research support from Pfizer and consultancy fees from AbbVie, GlaxoSmithKline, Merck, and Levicept. The other speaker disclosed working as an adviser to IBSA [Institut Biochimique SA], Sanofi, and Flexion Therapeutics; as an advisory board member for Laboratoires Genevrier and Labpharma; and receiving travel and accommodation support to attend the meeting from Nordic Pharma.
Office visit conversations are clues to teens’ predepressive symptoms
SAN FRANCISCO – if you know what to look for, suggest the findings of a qualitative study on teens’ sub-threshold symptoms of depression.
“Probing with sensitive questioning and understanding can help providers assess teens’ risks for depression,” said study coauthor Huma Khan, MD, of the University of Illinois Children’s Hospital in Chicago. “Furthermore, close follow-up with teens who mention certain topics, such as losing interest in activities or the loss of a loved one, also may help providers redirect the trajectory of depressive symptoms.”
To better understand ways in which teens may manifest sub-threshold depressive symptoms and possible coping mechanisms, Dr. Khan’s team conducted a qualitative analysis of 37 hour-long interviews with a subsample of teens enrolled in a larger study for adolescents at risk for depression. The teens, recruited from urban and suburban pediatric clinics, were aged 13-18 years and included 12 from Boston and 25 from Chicago. Ten were Hispanic, 15 were African American, and 12 were white.
The participants qualified for the study based on assessments using the Center for Epidemiological Studies Depression (CESD) scale and two questions about anhedonia and/or a depressed or irritable mood for at least 2 weeks. Teens with a current diagnosis of major depressive disorder or currently receiving therapy for depression were excluded.
Starting without a priori assumptions regarding potential findings, the researchers each independently used codes to identify key concepts in the transcripts and then categorized the codes. During regular meetings, they compared findings and continued until patterns in the content emerged.
The findings revealed that teens often express sadness in ways that don’t necessarily immediately call to mind a risk for depression.
“Our participants rarely described themselves as ‘depressed’ and instead used less specific terms such as ‘stressed’ or ‘down,’ ” Dr. Khan said. “Adolescents spoke of topics including unhappiness with school or family relationships that could be attributed to normal teenage angst by some. However, with further probing, adolescents revealed – in their own words – how profoundly impacted they were by their symptoms in various aspects of their lives.”
The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
The school pressures included difficulty understanding the material, completing work, passing classes, and achieving set goals. Problems with family ranged from tension and fighting to verbal and emotional abuse as well as stress from specific changes, such as divorce or frequent moves.
The researchers identified four main categories of sadness expression:
• Feeling stressed, sad, or down, often involving crying and interfering with their lives.
• Anger and irritability, often directed at others: One teen said, “Little things annoy me that used not to annoy me.”
• New feelings of apathy: One teen said, “I can still do the stuff I want to do, I just don’t feel like it. I used to love, love singing. Now, I sing, but I don’t really... it’s not all that.”
• Problems sleeping, including difficulty falling or staying asleep or sleeping too much.
“In contrast to the depression screening scales that only indicated sub-threshold depression, adolescents – with further questioning – spoke of significant symptoms of unhappiness, loss of interest in activities, and anger/irritability,” Dr. Khan said. “Some teens had little insight into their feelings.”
For example, statements made by the teens included, “They don’t understand why I’m upset. Sometimes I don’t either,” and “I just got really sad. I don’t know. You cry, but you don’t really know why you’re crying. You’re just crying.”
The adolescents told the researchers that spending time with friends was a major way of dealing with their feelings. In addition, two-thirds of the participants had a health issue that led them to visit their primary care provider or the emergency department. These conditions included asthma, allergies, thyroid issues, attention-deficit/hyperactivity disorder, migraines and headaches, arthritis, ulcers, abdominal pain, colonoscopy, fainting, acne, needing birth control pills, and panic attacks.
The researchers concluded that you need to tune into the feelings teens have through conversations about seemingly innocuous topics, whether it’s an annual check-up or an appointment for a specific concern. The statements and feelings expressed by the teens cut across ethnicities, indicating a possible “universality of symptoms for teens with predepression,” the researchers noted.
“The take-away message of our study is that adolescent providers can play an important role in the prevention of major depressive episodes by heavily relying on individual interviews with patients,” Dr. Khan said. “These conversations are powerful tools in uncovering psychological disturbances that may progress to debilitating depressive episodes if gone unnoticed.”
The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
SAN FRANCISCO – if you know what to look for, suggest the findings of a qualitative study on teens’ sub-threshold symptoms of depression.
“Probing with sensitive questioning and understanding can help providers assess teens’ risks for depression,” said study coauthor Huma Khan, MD, of the University of Illinois Children’s Hospital in Chicago. “Furthermore, close follow-up with teens who mention certain topics, such as losing interest in activities or the loss of a loved one, also may help providers redirect the trajectory of depressive symptoms.”
To better understand ways in which teens may manifest sub-threshold depressive symptoms and possible coping mechanisms, Dr. Khan’s team conducted a qualitative analysis of 37 hour-long interviews with a subsample of teens enrolled in a larger study for adolescents at risk for depression. The teens, recruited from urban and suburban pediatric clinics, were aged 13-18 years and included 12 from Boston and 25 from Chicago. Ten were Hispanic, 15 were African American, and 12 were white.
The participants qualified for the study based on assessments using the Center for Epidemiological Studies Depression (CESD) scale and two questions about anhedonia and/or a depressed or irritable mood for at least 2 weeks. Teens with a current diagnosis of major depressive disorder or currently receiving therapy for depression were excluded.
Starting without a priori assumptions regarding potential findings, the researchers each independently used codes to identify key concepts in the transcripts and then categorized the codes. During regular meetings, they compared findings and continued until patterns in the content emerged.
The findings revealed that teens often express sadness in ways that don’t necessarily immediately call to mind a risk for depression.
“Our participants rarely described themselves as ‘depressed’ and instead used less specific terms such as ‘stressed’ or ‘down,’ ” Dr. Khan said. “Adolescents spoke of topics including unhappiness with school or family relationships that could be attributed to normal teenage angst by some. However, with further probing, adolescents revealed – in their own words – how profoundly impacted they were by their symptoms in various aspects of their lives.”
The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
The school pressures included difficulty understanding the material, completing work, passing classes, and achieving set goals. Problems with family ranged from tension and fighting to verbal and emotional abuse as well as stress from specific changes, such as divorce or frequent moves.
The researchers identified four main categories of sadness expression:
• Feeling stressed, sad, or down, often involving crying and interfering with their lives.
• Anger and irritability, often directed at others: One teen said, “Little things annoy me that used not to annoy me.”
• New feelings of apathy: One teen said, “I can still do the stuff I want to do, I just don’t feel like it. I used to love, love singing. Now, I sing, but I don’t really... it’s not all that.”
• Problems sleeping, including difficulty falling or staying asleep or sleeping too much.
“In contrast to the depression screening scales that only indicated sub-threshold depression, adolescents – with further questioning – spoke of significant symptoms of unhappiness, loss of interest in activities, and anger/irritability,” Dr. Khan said. “Some teens had little insight into their feelings.”
For example, statements made by the teens included, “They don’t understand why I’m upset. Sometimes I don’t either,” and “I just got really sad. I don’t know. You cry, but you don’t really know why you’re crying. You’re just crying.”
The adolescents told the researchers that spending time with friends was a major way of dealing with their feelings. In addition, two-thirds of the participants had a health issue that led them to visit their primary care provider or the emergency department. These conditions included asthma, allergies, thyroid issues, attention-deficit/hyperactivity disorder, migraines and headaches, arthritis, ulcers, abdominal pain, colonoscopy, fainting, acne, needing birth control pills, and panic attacks.
The researchers concluded that you need to tune into the feelings teens have through conversations about seemingly innocuous topics, whether it’s an annual check-up or an appointment for a specific concern. The statements and feelings expressed by the teens cut across ethnicities, indicating a possible “universality of symptoms for teens with predepression,” the researchers noted.
“The take-away message of our study is that adolescent providers can play an important role in the prevention of major depressive episodes by heavily relying on individual interviews with patients,” Dr. Khan said. “These conversations are powerful tools in uncovering psychological disturbances that may progress to debilitating depressive episodes if gone unnoticed.”
The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
SAN FRANCISCO – if you know what to look for, suggest the findings of a qualitative study on teens’ sub-threshold symptoms of depression.
“Probing with sensitive questioning and understanding can help providers assess teens’ risks for depression,” said study coauthor Huma Khan, MD, of the University of Illinois Children’s Hospital in Chicago. “Furthermore, close follow-up with teens who mention certain topics, such as losing interest in activities or the loss of a loved one, also may help providers redirect the trajectory of depressive symptoms.”
To better understand ways in which teens may manifest sub-threshold depressive symptoms and possible coping mechanisms, Dr. Khan’s team conducted a qualitative analysis of 37 hour-long interviews with a subsample of teens enrolled in a larger study for adolescents at risk for depression. The teens, recruited from urban and suburban pediatric clinics, were aged 13-18 years and included 12 from Boston and 25 from Chicago. Ten were Hispanic, 15 were African American, and 12 were white.
The participants qualified for the study based on assessments using the Center for Epidemiological Studies Depression (CESD) scale and two questions about anhedonia and/or a depressed or irritable mood for at least 2 weeks. Teens with a current diagnosis of major depressive disorder or currently receiving therapy for depression were excluded.
Starting without a priori assumptions regarding potential findings, the researchers each independently used codes to identify key concepts in the transcripts and then categorized the codes. During regular meetings, they compared findings and continued until patterns in the content emerged.
The findings revealed that teens often express sadness in ways that don’t necessarily immediately call to mind a risk for depression.
“Our participants rarely described themselves as ‘depressed’ and instead used less specific terms such as ‘stressed’ or ‘down,’ ” Dr. Khan said. “Adolescents spoke of topics including unhappiness with school or family relationships that could be attributed to normal teenage angst by some. However, with further probing, adolescents revealed – in their own words – how profoundly impacted they were by their symptoms in various aspects of their lives.”
The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
The school pressures included difficulty understanding the material, completing work, passing classes, and achieving set goals. Problems with family ranged from tension and fighting to verbal and emotional abuse as well as stress from specific changes, such as divorce or frequent moves.
The researchers identified four main categories of sadness expression:
• Feeling stressed, sad, or down, often involving crying and interfering with their lives.
• Anger and irritability, often directed at others: One teen said, “Little things annoy me that used not to annoy me.”
• New feelings of apathy: One teen said, “I can still do the stuff I want to do, I just don’t feel like it. I used to love, love singing. Now, I sing, but I don’t really... it’s not all that.”
• Problems sleeping, including difficulty falling or staying asleep or sleeping too much.
“In contrast to the depression screening scales that only indicated sub-threshold depression, adolescents – with further questioning – spoke of significant symptoms of unhappiness, loss of interest in activities, and anger/irritability,” Dr. Khan said. “Some teens had little insight into their feelings.”
For example, statements made by the teens included, “They don’t understand why I’m upset. Sometimes I don’t either,” and “I just got really sad. I don’t know. You cry, but you don’t really know why you’re crying. You’re just crying.”
The adolescents told the researchers that spending time with friends was a major way of dealing with their feelings. In addition, two-thirds of the participants had a health issue that led them to visit their primary care provider or the emergency department. These conditions included asthma, allergies, thyroid issues, attention-deficit/hyperactivity disorder, migraines and headaches, arthritis, ulcers, abdominal pain, colonoscopy, fainting, acne, needing birth control pills, and panic attacks.
The researchers concluded that you need to tune into the feelings teens have through conversations about seemingly innocuous topics, whether it’s an annual check-up or an appointment for a specific concern. The statements and feelings expressed by the teens cut across ethnicities, indicating a possible “universality of symptoms for teens with predepression,” the researchers noted.
“The take-away message of our study is that adolescent providers can play an important role in the prevention of major depressive episodes by heavily relying on individual interviews with patients,” Dr. Khan said. “These conversations are powerful tools in uncovering psychological disturbances that may progress to debilitating depressive episodes if gone unnoticed.”
The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
AT PAS 17
Key clinical point: Dialogue with teens at each visit may reveal predepressive symptoms indicating an opportunity for depression prevention.
Major finding: The research identified themes in three areas: external negative sources of stress, expressions of sadness, and coping practices. The three main sources of external stress identified included school pressure, family discord, and death of a close friend or family member.
Data source: The findings are based on a qualitative analysis of 37 K-SADS interviews with teens aged 13-18 years from Chicago and Boston community pediatric clinics.
Disclosures: The research was funded by the National Institutes of Mental Health. Dr. Khan had no relevant financial disclosures.
Expert: Engage patients, clinicians as partners in research
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
[email protected]
On Twitter @whitneymcknight
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
[email protected]
On Twitter @whitneymcknight
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
[email protected]
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
Preventing Zika in pregnancy: What you need to know
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Asymptomatic maternal Zika infection doesn’t dampen birth defect risk
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at [email protected].
[email protected]
On Twitter @ObGynNews
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at [email protected].
[email protected]
On Twitter @ObGynNews
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at [email protected].
[email protected]
On Twitter @ObGynNews
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
What is the best approach for managing CIED infections?
The case
A 72-year-old man with ischemic cardiomyopathy and left-ventricular ejection fraction of 15% had an cardioverter-defibrillator implanted five years ago for primary prevention of sudden cardiac death. He was brought to the emergency department by his daughter who noticed erythema and swelling over the generator pocket site. His temperature is 100.1° F. Vital signs are otherwise normal and stable.
What are the best initial and definitive management strategies for this patient?
When should a cardiac implanted electronic device (CIED) infection be suspected?
CIED infections generally present in one of two ways: as a local generator pocket infection or as a systemic illness.1 Around 70% of CIED infections present with findings related to the generator pocket site. Findings in such cases include pain, swelling, erythema, induration, and ulceration. Systemic findings range from vague constitutional symptoms to overt sepsis. It is important to note that systemic signs of infection are only present in the minority of cases. Their absence does not rule out a CIED infection.1,2 As such, hospitalists must maintain a high index of suspicion in order to avoid missing the diagnosis.
Unfortunately, it can be difficult to distinguish between a CIED infection and less severe postimplantation complications such as surgical site infections, superficial pocket site infections, and noninfected hematoma.2
What are the risk factors for CIED infections?
The risk factors for CIED infection fit into three broad categories: procedure, patient, and pathogen.
Procedural factors that increase risk of infection include lack of periprocedural antimicrobial prophylaxis, inexperienced physician operator, multiple revision procedures, hematoma formation at the pocket site, and increased amount of hardware.1
Patient factors center on medical comorbidities, including congestive heart failure, diabetes mellitus, chronic kidney disease, immunosuppression, and ongoing oral anticoagulation.1
The specific pathogen also plays a role in infection risk. In one cohort study of 1,524 patients with CIEDs, patients with Staphylococcus aureus bacteremia ended up having confirmed or suspected CIED infections in 54.6% of cases, compared with just 12.0% of patients who had bacteremia with gram-negative bacilli.3
Which bacteria cause most CIED infections?
The vast majority of CIED infections are caused by gram-positive bacteria.1,4 An Italian study of 1,204 patients with CIED infection reported that pathogens isolated from extracted leads were gram-positive bacteria in 92.5% of infections.4 Staph species are the most common pathogens. Coagulase-negative staphylococcus and Staphylococcus aureus accounted for 69% and 13.8% of all isolates, respectively. Of note, 33% of CoNS isolates and 13% of S. aureus isolates were resistant to oxacillin in that study.4
Which initial diagnostic tests should be performed?
Patients should have two sets of blood cultures drawn from two separate sites, prior to administration of antibiotics.1 Current guidelines recommend against aspiration of a suspected infected pocket site because the sensitivity for identifying the causal pathogen is low while the risk of introducing infection to the generator pocket is substantial.1 In the event of CIED removal, pocket tissue and lead tips should be sent for gram stain and culture.1
Do all patients require a transesophageal echocardiogram?
Guidelines recommend a transesophageal echocardiogram (TEE) if suspicion for CIED infection is high based on positive blood cultures, antibiotic initiation prior to culture collection, ongoing systemic illness, or other suggestive signs.1,2 Positive transthoracic echocardiogram findings (for example, a valve vegetation) do not obviate the need for TEE because of the possibility of other relevant complications (including endocarditis and perivalvular extension) for which TEE has a greater sensitivity.1
What is the approach to antimicrobial therapy?
Since most infections involve staphylococcus species, initial empiric antimicrobial therapy should cover both oxacillin-sensitive and oxacillin-resistant strains. Thus, intravenous vancomycin is an appropriate initial choice.1 Culture and sensitivity results should then guide specific therapy decisions.1 Table 1 provides a summary of strategies for antimicrobial selection and duration.
Should all patients undergo complete device removal?
All patients with CIED infection require complete device removal, even if the infection is suspected to be confined to the generator pocket and blood cultures remain negative.2 Patients with superficial or surgical site infections without CIED infection do not require complete device removal. Rather, those cases can be managed with a 7- to 10-day course of oral antimicrobials.1
After device removal, what is the appropriate timing for installing a new device?
The decision to implant a replacement device is often made with input from infectious disease and cardiac electrophysiology experts. The decision must consider both infection and device-related concerns. Importantly, repeat blood cultures must be negative, and any infection in the pocket site should be controlled prior to installing a new device.2
Should all patients with a CIED receive antimicrobial prophylaxis prior to invasive dental, urologic, or endoscopic procedures?
No. Merely having a CIED is not considered an indication for antimicrobial prophylaxis.2
Back to the case
Two sets of blood cultures are drawn, and vancomycin is started as empiric therapy. The culture results show CoNS species, and antimicrobial resistance testing shows oxacillin-resistance.
TEE shows a vegetation on one of the leads but no vegetation on any of the heart valves. Cardiac electrophysiology is consulted and performs a percutaneous extraction of the entire device (generator and leads). Starting on the day of extraction, the patient undergoes two weeks of intravenous antimicrobial therapy with vancomycin. The patient, his family, and the electrophysiology team discuss the patient’s wishes, indications, and potential burdens related to device replacement.
He ultimately decides to have a replacement device installed. An infectious disease specialist is consulted to help define appropriate timing of the new device installation procedure.
Bottom line
The patient clearly had a CIED infection which required TEE, extraction of his CIED, and prolonged antimicrobial therapy.
Dr. Davisson is a primary care physician at Community Health Network in Indianapolis, Ind. Dr. Lockwood is a hospitalist at the Lexington VA Medical Center. Dr. Sweigart is a hospitalist at the University of Kentucky, Lexington, and the Lexington VA Medical Center.
References
1. Baddour LM, Epstein AE, Erickson CC, et al. Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association. Circulation. 2010;121(3):458-77.
2. Baddour LM, Cha YM, Wilson WR. Infections of Cardiovascular Implantable Electronic Devices. N Engl J Med. 2012;367(9):842-9.
3. Uslan DZ, Sohail MR, St. Sauver JL, et al. Permanent Pacemaker and Implantable Cardioverter Defibrillator Infection: A Population-Based Study. Arch Intern Med. 2007;167(7):669-75.
4. Bongiorni MG, Tascini C, Tagliaferri E, et al. Microbiology of Cardiac Implantable Electronic Device Infections. Europace. 2012;14(9):1334-9.
The case
A 72-year-old man with ischemic cardiomyopathy and left-ventricular ejection fraction of 15% had an cardioverter-defibrillator implanted five years ago for primary prevention of sudden cardiac death. He was brought to the emergency department by his daughter who noticed erythema and swelling over the generator pocket site. His temperature is 100.1° F. Vital signs are otherwise normal and stable.
What are the best initial and definitive management strategies for this patient?
When should a cardiac implanted electronic device (CIED) infection be suspected?
CIED infections generally present in one of two ways: as a local generator pocket infection or as a systemic illness.1 Around 70% of CIED infections present with findings related to the generator pocket site. Findings in such cases include pain, swelling, erythema, induration, and ulceration. Systemic findings range from vague constitutional symptoms to overt sepsis. It is important to note that systemic signs of infection are only present in the minority of cases. Their absence does not rule out a CIED infection.1,2 As such, hospitalists must maintain a high index of suspicion in order to avoid missing the diagnosis.
Unfortunately, it can be difficult to distinguish between a CIED infection and less severe postimplantation complications such as surgical site infections, superficial pocket site infections, and noninfected hematoma.2
What are the risk factors for CIED infections?
The risk factors for CIED infection fit into three broad categories: procedure, patient, and pathogen.
Procedural factors that increase risk of infection include lack of periprocedural antimicrobial prophylaxis, inexperienced physician operator, multiple revision procedures, hematoma formation at the pocket site, and increased amount of hardware.1
Patient factors center on medical comorbidities, including congestive heart failure, diabetes mellitus, chronic kidney disease, immunosuppression, and ongoing oral anticoagulation.1
The specific pathogen also plays a role in infection risk. In one cohort study of 1,524 patients with CIEDs, patients with Staphylococcus aureus bacteremia ended up having confirmed or suspected CIED infections in 54.6% of cases, compared with just 12.0% of patients who had bacteremia with gram-negative bacilli.3
Which bacteria cause most CIED infections?
The vast majority of CIED infections are caused by gram-positive bacteria.1,4 An Italian study of 1,204 patients with CIED infection reported that pathogens isolated from extracted leads were gram-positive bacteria in 92.5% of infections.4 Staph species are the most common pathogens. Coagulase-negative staphylococcus and Staphylococcus aureus accounted for 69% and 13.8% of all isolates, respectively. Of note, 33% of CoNS isolates and 13% of S. aureus isolates were resistant to oxacillin in that study.4
Which initial diagnostic tests should be performed?
Patients should have two sets of blood cultures drawn from two separate sites, prior to administration of antibiotics.1 Current guidelines recommend against aspiration of a suspected infected pocket site because the sensitivity for identifying the causal pathogen is low while the risk of introducing infection to the generator pocket is substantial.1 In the event of CIED removal, pocket tissue and lead tips should be sent for gram stain and culture.1
Do all patients require a transesophageal echocardiogram?
Guidelines recommend a transesophageal echocardiogram (TEE) if suspicion for CIED infection is high based on positive blood cultures, antibiotic initiation prior to culture collection, ongoing systemic illness, or other suggestive signs.1,2 Positive transthoracic echocardiogram findings (for example, a valve vegetation) do not obviate the need for TEE because of the possibility of other relevant complications (including endocarditis and perivalvular extension) for which TEE has a greater sensitivity.1
What is the approach to antimicrobial therapy?
Since most infections involve staphylococcus species, initial empiric antimicrobial therapy should cover both oxacillin-sensitive and oxacillin-resistant strains. Thus, intravenous vancomycin is an appropriate initial choice.1 Culture and sensitivity results should then guide specific therapy decisions.1 Table 1 provides a summary of strategies for antimicrobial selection and duration.
Should all patients undergo complete device removal?
All patients with CIED infection require complete device removal, even if the infection is suspected to be confined to the generator pocket and blood cultures remain negative.2 Patients with superficial or surgical site infections without CIED infection do not require complete device removal. Rather, those cases can be managed with a 7- to 10-day course of oral antimicrobials.1
After device removal, what is the appropriate timing for installing a new device?
The decision to implant a replacement device is often made with input from infectious disease and cardiac electrophysiology experts. The decision must consider both infection and device-related concerns. Importantly, repeat blood cultures must be negative, and any infection in the pocket site should be controlled prior to installing a new device.2
Should all patients with a CIED receive antimicrobial prophylaxis prior to invasive dental, urologic, or endoscopic procedures?
No. Merely having a CIED is not considered an indication for antimicrobial prophylaxis.2
Back to the case
Two sets of blood cultures are drawn, and vancomycin is started as empiric therapy. The culture results show CoNS species, and antimicrobial resistance testing shows oxacillin-resistance.
TEE shows a vegetation on one of the leads but no vegetation on any of the heart valves. Cardiac electrophysiology is consulted and performs a percutaneous extraction of the entire device (generator and leads). Starting on the day of extraction, the patient undergoes two weeks of intravenous antimicrobial therapy with vancomycin. The patient, his family, and the electrophysiology team discuss the patient’s wishes, indications, and potential burdens related to device replacement.
He ultimately decides to have a replacement device installed. An infectious disease specialist is consulted to help define appropriate timing of the new device installation procedure.
Bottom line
The patient clearly had a CIED infection which required TEE, extraction of his CIED, and prolonged antimicrobial therapy.
Dr. Davisson is a primary care physician at Community Health Network in Indianapolis, Ind. Dr. Lockwood is a hospitalist at the Lexington VA Medical Center. Dr. Sweigart is a hospitalist at the University of Kentucky, Lexington, and the Lexington VA Medical Center.
References
1. Baddour LM, Epstein AE, Erickson CC, et al. Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association. Circulation. 2010;121(3):458-77.
2. Baddour LM, Cha YM, Wilson WR. Infections of Cardiovascular Implantable Electronic Devices. N Engl J Med. 2012;367(9):842-9.
3. Uslan DZ, Sohail MR, St. Sauver JL, et al. Permanent Pacemaker and Implantable Cardioverter Defibrillator Infection: A Population-Based Study. Arch Intern Med. 2007;167(7):669-75.
4. Bongiorni MG, Tascini C, Tagliaferri E, et al. Microbiology of Cardiac Implantable Electronic Device Infections. Europace. 2012;14(9):1334-9.
The case
A 72-year-old man with ischemic cardiomyopathy and left-ventricular ejection fraction of 15% had an cardioverter-defibrillator implanted five years ago for primary prevention of sudden cardiac death. He was brought to the emergency department by his daughter who noticed erythema and swelling over the generator pocket site. His temperature is 100.1° F. Vital signs are otherwise normal and stable.
What are the best initial and definitive management strategies for this patient?
When should a cardiac implanted electronic device (CIED) infection be suspected?
CIED infections generally present in one of two ways: as a local generator pocket infection or as a systemic illness.1 Around 70% of CIED infections present with findings related to the generator pocket site. Findings in such cases include pain, swelling, erythema, induration, and ulceration. Systemic findings range from vague constitutional symptoms to overt sepsis. It is important to note that systemic signs of infection are only present in the minority of cases. Their absence does not rule out a CIED infection.1,2 As such, hospitalists must maintain a high index of suspicion in order to avoid missing the diagnosis.
Unfortunately, it can be difficult to distinguish between a CIED infection and less severe postimplantation complications such as surgical site infections, superficial pocket site infections, and noninfected hematoma.2
What are the risk factors for CIED infections?
The risk factors for CIED infection fit into three broad categories: procedure, patient, and pathogen.
Procedural factors that increase risk of infection include lack of periprocedural antimicrobial prophylaxis, inexperienced physician operator, multiple revision procedures, hematoma formation at the pocket site, and increased amount of hardware.1
Patient factors center on medical comorbidities, including congestive heart failure, diabetes mellitus, chronic kidney disease, immunosuppression, and ongoing oral anticoagulation.1
The specific pathogen also plays a role in infection risk. In one cohort study of 1,524 patients with CIEDs, patients with Staphylococcus aureus bacteremia ended up having confirmed or suspected CIED infections in 54.6% of cases, compared with just 12.0% of patients who had bacteremia with gram-negative bacilli.3
Which bacteria cause most CIED infections?
The vast majority of CIED infections are caused by gram-positive bacteria.1,4 An Italian study of 1,204 patients with CIED infection reported that pathogens isolated from extracted leads were gram-positive bacteria in 92.5% of infections.4 Staph species are the most common pathogens. Coagulase-negative staphylococcus and Staphylococcus aureus accounted for 69% and 13.8% of all isolates, respectively. Of note, 33% of CoNS isolates and 13% of S. aureus isolates were resistant to oxacillin in that study.4
Which initial diagnostic tests should be performed?
Patients should have two sets of blood cultures drawn from two separate sites, prior to administration of antibiotics.1 Current guidelines recommend against aspiration of a suspected infected pocket site because the sensitivity for identifying the causal pathogen is low while the risk of introducing infection to the generator pocket is substantial.1 In the event of CIED removal, pocket tissue and lead tips should be sent for gram stain and culture.1
Do all patients require a transesophageal echocardiogram?
Guidelines recommend a transesophageal echocardiogram (TEE) if suspicion for CIED infection is high based on positive blood cultures, antibiotic initiation prior to culture collection, ongoing systemic illness, or other suggestive signs.1,2 Positive transthoracic echocardiogram findings (for example, a valve vegetation) do not obviate the need for TEE because of the possibility of other relevant complications (including endocarditis and perivalvular extension) for which TEE has a greater sensitivity.1
What is the approach to antimicrobial therapy?
Since most infections involve staphylococcus species, initial empiric antimicrobial therapy should cover both oxacillin-sensitive and oxacillin-resistant strains. Thus, intravenous vancomycin is an appropriate initial choice.1 Culture and sensitivity results should then guide specific therapy decisions.1 Table 1 provides a summary of strategies for antimicrobial selection and duration.
Should all patients undergo complete device removal?
All patients with CIED infection require complete device removal, even if the infection is suspected to be confined to the generator pocket and blood cultures remain negative.2 Patients with superficial or surgical site infections without CIED infection do not require complete device removal. Rather, those cases can be managed with a 7- to 10-day course of oral antimicrobials.1
After device removal, what is the appropriate timing for installing a new device?
The decision to implant a replacement device is often made with input from infectious disease and cardiac electrophysiology experts. The decision must consider both infection and device-related concerns. Importantly, repeat blood cultures must be negative, and any infection in the pocket site should be controlled prior to installing a new device.2
Should all patients with a CIED receive antimicrobial prophylaxis prior to invasive dental, urologic, or endoscopic procedures?
No. Merely having a CIED is not considered an indication for antimicrobial prophylaxis.2
Back to the case
Two sets of blood cultures are drawn, and vancomycin is started as empiric therapy. The culture results show CoNS species, and antimicrobial resistance testing shows oxacillin-resistance.
TEE shows a vegetation on one of the leads but no vegetation on any of the heart valves. Cardiac electrophysiology is consulted and performs a percutaneous extraction of the entire device (generator and leads). Starting on the day of extraction, the patient undergoes two weeks of intravenous antimicrobial therapy with vancomycin. The patient, his family, and the electrophysiology team discuss the patient’s wishes, indications, and potential burdens related to device replacement.
He ultimately decides to have a replacement device installed. An infectious disease specialist is consulted to help define appropriate timing of the new device installation procedure.
Bottom line
The patient clearly had a CIED infection which required TEE, extraction of his CIED, and prolonged antimicrobial therapy.
Dr. Davisson is a primary care physician at Community Health Network in Indianapolis, Ind. Dr. Lockwood is a hospitalist at the Lexington VA Medical Center. Dr. Sweigart is a hospitalist at the University of Kentucky, Lexington, and the Lexington VA Medical Center.
References
1. Baddour LM, Epstein AE, Erickson CC, et al. Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association. Circulation. 2010;121(3):458-77.
2. Baddour LM, Cha YM, Wilson WR. Infections of Cardiovascular Implantable Electronic Devices. N Engl J Med. 2012;367(9):842-9.
3. Uslan DZ, Sohail MR, St. Sauver JL, et al. Permanent Pacemaker and Implantable Cardioverter Defibrillator Infection: A Population-Based Study. Arch Intern Med. 2007;167(7):669-75.
4. Bongiorni MG, Tascini C, Tagliaferri E, et al. Microbiology of Cardiac Implantable Electronic Device Infections. Europace. 2012;14(9):1334-9.
Stressful life events take greater cognitive toll on African Americans than whites
LONDON – African Americans not only report experiencing more stressful experiences across their lifespans than do whites, but they have more cognitive consequences from them as well, new research suggests.
In fact, the weight of these experiences affected cognition even more than traditional risk factors like genetic status and even age, Megan Zuelsdorff, PhD, said at the Alzheimer’s Association International Conference.
Racial disparities have long been evident in the development and progression of dementia, Dr. Zuelsdorff said. Socioeconomic factors are also important players in this scenario. Stress, likewise, has long been linked to poorer cognitive health. “But, there are still significant gaps in our knowledge of stress and cognition. The contribution of stress to well-established socioeconomic impacts on health is unclear, and the research focus here has always been on events happening in midlife and onward. But, it’s crucial to expand this window of time backward to include earlier years. If we look at a graph of cognitive function across the lifespan, the rate of decline doesn’t vary much. What we do see is that blacks, starting at midlife, are closer to the clinical threshold of cognitive impairment and may reach the threshold at an earlier age. What this said to me is that we needed to look at these earlier life factors that could bring someone to this state of lower cognitive function in midlife.”
Dr. Zuelsdorff and her colleagues analyzed data from the Wisconsin Registry for Alzheimer’s Prevention to examine this question. The observational study comprises 1,500 adults being followed for 15-20 years and is enriched for those with a family history of Alzheimer’s disease. The main goal of WRAP is to understand the biological, medical, environmental, and lifestyle factors that increase a person’s risk of developing Alzheimer’s disease.
Subjects have a study visit every 2-4 years that includes a full physical and cognitive workup. At one visit, Dr. Zuelsdorff said, they were asked to complete a questionnaire concerning 27 different stressful life events. These experiences were deeply disturbing and potentially life altering. They included childhood experiences, such as parental abuse, alcoholism, and flunking out of school, and adult experiences, such as combat experience, bankruptcy, or the death of a child. She then analyzed how the total number of stressful events in a person’s life changed that person’s risk of developing dementia.
Of the entire WRAP cohort, 1,314 completed the stress questionnaire and had sufficient cognitive data. These subjects were largely white (1,232). Only 82 were African American, a weakness of the study, Dr. Zuelsdorff noted, but a reflection of Wisconsin’s racial makeup.
They were similar in a number of important ways, including age (mean, 58 years), proportion of apolipoprotein E4 (APOE4) allele carriers (38%), and years of education (mean, 16). African Americans had higher body mass index (33.3 vs. 28.8 kg/m2), reported less physical activity, were more often current smokers (22% vs. 6%), and had a lower-quality education despite similar time in the classroom.
On average, African Americans reported a mean of 4.5 stressful life events – a significant, 60% increase over the 2.8 reported by whites. The experience of stressful events directly influenced a subject’s performance in the speed and flexibility domain of executive function and in working memory, Dr. Zuelsdorff said.
“We saw a substantial 13.5% attenuation of performance on speed and flexibility, but we also saw attenuation in working memory. That told us something else was going on – that it wasn’t just the accumulation of stressful events but that there was a differential vulnerability. The negative association between lifetime stressful events and the cognitive domains was much stronger in blacks than in whites.”
She then conducted a risk analysis to determine the impact of stress. “Stress was right at the top for blacks. It tended to be one of the most important predictors of cognitive function. The only other one that came out as significant was quality of education. The social environment in this sample was more important than the traditional risk factors of genetics and chronological age.”
The study barely scratches the surface of the stress/cognition conundrum, Dr. Zuelsdorff said. “We would like to look at the timing next and see if there is some critical window that is especially influencing to cognitive health. We then need to target both interventions and effect modifiers, such as social, community, and financial resources that might buffer the effects of this negative stress.”
She had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – African Americans not only report experiencing more stressful experiences across their lifespans than do whites, but they have more cognitive consequences from them as well, new research suggests.
In fact, the weight of these experiences affected cognition even more than traditional risk factors like genetic status and even age, Megan Zuelsdorff, PhD, said at the Alzheimer’s Association International Conference.
Racial disparities have long been evident in the development and progression of dementia, Dr. Zuelsdorff said. Socioeconomic factors are also important players in this scenario. Stress, likewise, has long been linked to poorer cognitive health. “But, there are still significant gaps in our knowledge of stress and cognition. The contribution of stress to well-established socioeconomic impacts on health is unclear, and the research focus here has always been on events happening in midlife and onward. But, it’s crucial to expand this window of time backward to include earlier years. If we look at a graph of cognitive function across the lifespan, the rate of decline doesn’t vary much. What we do see is that blacks, starting at midlife, are closer to the clinical threshold of cognitive impairment and may reach the threshold at an earlier age. What this said to me is that we needed to look at these earlier life factors that could bring someone to this state of lower cognitive function in midlife.”
Dr. Zuelsdorff and her colleagues analyzed data from the Wisconsin Registry for Alzheimer’s Prevention to examine this question. The observational study comprises 1,500 adults being followed for 15-20 years and is enriched for those with a family history of Alzheimer’s disease. The main goal of WRAP is to understand the biological, medical, environmental, and lifestyle factors that increase a person’s risk of developing Alzheimer’s disease.
Subjects have a study visit every 2-4 years that includes a full physical and cognitive workup. At one visit, Dr. Zuelsdorff said, they were asked to complete a questionnaire concerning 27 different stressful life events. These experiences were deeply disturbing and potentially life altering. They included childhood experiences, such as parental abuse, alcoholism, and flunking out of school, and adult experiences, such as combat experience, bankruptcy, or the death of a child. She then analyzed how the total number of stressful events in a person’s life changed that person’s risk of developing dementia.
Of the entire WRAP cohort, 1,314 completed the stress questionnaire and had sufficient cognitive data. These subjects were largely white (1,232). Only 82 were African American, a weakness of the study, Dr. Zuelsdorff noted, but a reflection of Wisconsin’s racial makeup.
They were similar in a number of important ways, including age (mean, 58 years), proportion of apolipoprotein E4 (APOE4) allele carriers (38%), and years of education (mean, 16). African Americans had higher body mass index (33.3 vs. 28.8 kg/m2), reported less physical activity, were more often current smokers (22% vs. 6%), and had a lower-quality education despite similar time in the classroom.
On average, African Americans reported a mean of 4.5 stressful life events – a significant, 60% increase over the 2.8 reported by whites. The experience of stressful events directly influenced a subject’s performance in the speed and flexibility domain of executive function and in working memory, Dr. Zuelsdorff said.
“We saw a substantial 13.5% attenuation of performance on speed and flexibility, but we also saw attenuation in working memory. That told us something else was going on – that it wasn’t just the accumulation of stressful events but that there was a differential vulnerability. The negative association between lifetime stressful events and the cognitive domains was much stronger in blacks than in whites.”
She then conducted a risk analysis to determine the impact of stress. “Stress was right at the top for blacks. It tended to be one of the most important predictors of cognitive function. The only other one that came out as significant was quality of education. The social environment in this sample was more important than the traditional risk factors of genetics and chronological age.”
The study barely scratches the surface of the stress/cognition conundrum, Dr. Zuelsdorff said. “We would like to look at the timing next and see if there is some critical window that is especially influencing to cognitive health. We then need to target both interventions and effect modifiers, such as social, community, and financial resources that might buffer the effects of this negative stress.”
She had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – African Americans not only report experiencing more stressful experiences across their lifespans than do whites, but they have more cognitive consequences from them as well, new research suggests.
In fact, the weight of these experiences affected cognition even more than traditional risk factors like genetic status and even age, Megan Zuelsdorff, PhD, said at the Alzheimer’s Association International Conference.
Racial disparities have long been evident in the development and progression of dementia, Dr. Zuelsdorff said. Socioeconomic factors are also important players in this scenario. Stress, likewise, has long been linked to poorer cognitive health. “But, there are still significant gaps in our knowledge of stress and cognition. The contribution of stress to well-established socioeconomic impacts on health is unclear, and the research focus here has always been on events happening in midlife and onward. But, it’s crucial to expand this window of time backward to include earlier years. If we look at a graph of cognitive function across the lifespan, the rate of decline doesn’t vary much. What we do see is that blacks, starting at midlife, are closer to the clinical threshold of cognitive impairment and may reach the threshold at an earlier age. What this said to me is that we needed to look at these earlier life factors that could bring someone to this state of lower cognitive function in midlife.”
Dr. Zuelsdorff and her colleagues analyzed data from the Wisconsin Registry for Alzheimer’s Prevention to examine this question. The observational study comprises 1,500 adults being followed for 15-20 years and is enriched for those with a family history of Alzheimer’s disease. The main goal of WRAP is to understand the biological, medical, environmental, and lifestyle factors that increase a person’s risk of developing Alzheimer’s disease.
Subjects have a study visit every 2-4 years that includes a full physical and cognitive workup. At one visit, Dr. Zuelsdorff said, they were asked to complete a questionnaire concerning 27 different stressful life events. These experiences were deeply disturbing and potentially life altering. They included childhood experiences, such as parental abuse, alcoholism, and flunking out of school, and adult experiences, such as combat experience, bankruptcy, or the death of a child. She then analyzed how the total number of stressful events in a person’s life changed that person’s risk of developing dementia.
Of the entire WRAP cohort, 1,314 completed the stress questionnaire and had sufficient cognitive data. These subjects were largely white (1,232). Only 82 were African American, a weakness of the study, Dr. Zuelsdorff noted, but a reflection of Wisconsin’s racial makeup.
They were similar in a number of important ways, including age (mean, 58 years), proportion of apolipoprotein E4 (APOE4) allele carriers (38%), and years of education (mean, 16). African Americans had higher body mass index (33.3 vs. 28.8 kg/m2), reported less physical activity, were more often current smokers (22% vs. 6%), and had a lower-quality education despite similar time in the classroom.
On average, African Americans reported a mean of 4.5 stressful life events – a significant, 60% increase over the 2.8 reported by whites. The experience of stressful events directly influenced a subject’s performance in the speed and flexibility domain of executive function and in working memory, Dr. Zuelsdorff said.
“We saw a substantial 13.5% attenuation of performance on speed and flexibility, but we also saw attenuation in working memory. That told us something else was going on – that it wasn’t just the accumulation of stressful events but that there was a differential vulnerability. The negative association between lifetime stressful events and the cognitive domains was much stronger in blacks than in whites.”
She then conducted a risk analysis to determine the impact of stress. “Stress was right at the top for blacks. It tended to be one of the most important predictors of cognitive function. The only other one that came out as significant was quality of education. The social environment in this sample was more important than the traditional risk factors of genetics and chronological age.”
The study barely scratches the surface of the stress/cognition conundrum, Dr. Zuelsdorff said. “We would like to look at the timing next and see if there is some critical window that is especially influencing to cognitive health. We then need to target both interventions and effect modifiers, such as social, community, and financial resources that might buffer the effects of this negative stress.”
She had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: African Americans reported 60% more stressful life events than whites, which were tied to a 13% decrease in the speed and flexibility domain of executive function.
Data source: The observational cohort study comprised 1,314 subjects.
Disclosures: Dr. Zuelsdorff had no financial disclosures.
Symptoms Mimicking Those of Hypokalemic Periodic Paralysis Induced by Soluble Barium Poisoning
Hypokalemic periodic paralysis (HPP) is a relatively common and potentially life-threating condition that can be either sporadic or recurring and has both inherited and acquired causes.1 Familial HPP, on the other hand, is a rare condition (1:100,000) caused by loss of function mutations leading to the disruption of membrane potential consequently making them inexcitable.2 Appearance of symptoms is typically in the first or second decade of life (60% of cases have onset aged < 16 years) with susceptible individuals experiencing sudden onset of perioral numbness; weakness; centrifugal paralysis, often with nausea; vomiting and diarrhea; and prostration, usually triggered by highcarbohydrate meals and rest following sustained muscle-group use.3
These symptoms are common to all forms of HPP, making the differential diagnosis wide and confusing. Rhabdomyolysis is occasionally associated with many severe hypokalemic episodes.4 Myopathy and permanent muscle weakness have been reported in HPP.5,6 Other reported inciting factors include a drop in serum potassium caused by β-adrenergic bronchodilator treatment.7 Clinical attacks also have been associated with diabetic ketoacidosis and combined hypokalemia and hypophosphatemia.8 Thyrotoxicosis also causes similar muscle action potential changes but only when hyperthyroidism is uncorrected. 9-12 Less commonly, hypothyroidism has been reported to be associated with hypokalemic paralysis.3
Pa Ping, a condition involving hypokalemic paralysis of uncertain etiology, is geographically centered in the Szechuan region of China.13 Cases of Bartter, Liddle, and Gitelman syndromes also have been associated with hypokalemic paralysis.3,14 There is an association with malignant hyperthermia following or during systemic anesthesia. Patients presenting as Guillain-Barré syndrome have been found to have periodic paralysis triggered by hypokalemia from any cause.15 Sjögren syndrome and renal tubular acidosis also are reported to have triggered symptoms of hypokalemic paralysis.16,17
True type 1 HPP is caused by channelopathies resulting from mutations in the calcium channel gene CACN1AS (HypoPP1), which accounts for 70% of the cases, whereas type 2 HPP is cause by sodium channel gene SCN4A (HypoPP2) mutations, which accounts for 10% to 20% of cases.18,19 An association with a voltage-gated potassium channel KCNE3 mutation has been made but is disputed.20,21 Females typically have less severe and less frequent attacks, and attacks lessen or disappear during pregnancy.22
In a small controlled trial, acetazolamide has been reported to have prophylactic benefit, although a more powerful carbonic anhydrase inhibitor, dichlorophenamide, was reported to be effective in a study after acetazolamide had become ineffective.23,24 These treatments would not be expected to be of clinical use in hypokalemia due to barium poisoning.
Barium poisoning has been reported as a result of accidental contamination of foodstuffs with soluble barium.25 Onset of symptoms is rapid, with nausea, vomiting, diarrhea, and malaise followed rapidly by weakness, which can include the muscles of respiration. This littleconsidered but rapidly lethal poisoning event can be accidental as a result of environmental exposure due to unintentional ingestion of the toxin or deliberate criminal poisoning as in this case. Because deliberate poisoning rarely crosses the mind of the clinician, awareness of the potential similarity of barium poisoning to other forms of HPP and even familial HPP is important.
Case Presentation
A male veteran aged 45 years when treated by the authors was well until moving into a new rural home when he began to experience acute episodes of variable perioral numbness, diarrhea, paresthesias, abdominal cramping, and weakness, which ranged from mild, self-terminating extremity weakness to 3 episodes of respiratory failure that required intubation and mechanical ventilation.
All episodes were accompanied by hypokalemia in the range of 2 to 3 mEq/L, but levels varied erratically during admissions from severe hypokalemia to normo- and hyperkalemia. Over 3 years, the patient was admitted to the hospital 19 times, underwent extensive workup, and was referred to endocrinology services at Duke University, Vanderbilt University, and the Cleveland Clinic. Diagnostic efforts centered on establishing whether he had a latepresenting variant of familial HPP.
Genetic evaluations could not identify known single-nucleotide polymorphisms associated with that condition. The consensus was that he had a potassium leak somewhere between his kidneys and bladder. Recommended management was a high baseline oral potassium supplementation and spironolactone. He had a brief period of improvement after moving to a different house, but the episodes returned once he moved back to his old house despite adherence to recommended treatment. In December 2012, he experienced his worst episode, with potassium 1.8 mEq/L on admission, resulting in admission to the intensive care unit (ICU).
Following a precipitous clinical decline, the patient was intubated and mechanically ventilated. Nephrology was consulted and given the recurrent life-threatening pattern, an intensive chart review was undertaken. It was noted that a urine arsenic level that had been normal several admissions previously at 18 μg/L was elevated during a subsequent admission at 59 μg/L, and several weeks later during a later admission the level had fallen to 15 μg/L. Urine lead was undetectable on 3 occasions, and urine mercury was within normal limits.
Arsenic toxicity did not match the patient’s clinical syndrome, but the pattern seemed to be consistent with the possibility of unexplained toxic exposure and subsequent clearance. Therefore, an intensive literature search for syndromes of environmental exposure or poisoning resembling HPP was undertaken. The search revealed several references in the literature to paralysis similar to HPP that involved ingestion of hair-removing soap and rat poison containing barium sulfide and carbonate. References also pointed to the similarity of the symptoms to Guillain-Barre syndrome.
As a result of that literature search, a blood barium level was collected in the ICU that revealed 14,550 ng/mL. A scalp hair sample showed 6.1 μg barium per gram of hair (reference, 0.53 μg/g to 2 μg/g). Neither the patient nor his wife reported being involved in painting, ceramic work, decorating glassware or fabric with dyes, working with stained glass, smelting, metal welding, or use of vermicides.
A U.S. Environmental Protection Agency team was sent to the house, and a detailed toxic survey of the house and the surrounding grounds was conducted with no excess barium found. Barium levels were checked by a private physician on the wife and 2 minor children. The wife’s barium levels came back undetectable in a blood sample and elevated in a hair sample. One child had a very low detected level in her blood and slightly elevated in her hair, and the other child had a low level in her blood and her hair. Because the circumstances of the wife’s and children’s exposure could not be explained environmentally nor could the veteran’s exposure source be identified, the VA Police Service contacted the Tennessee Bureau of Investigation, and they questioned the veteran and his wife.
Shortly after that the veteran received a paralyzing gunshot wound to the back, and the ensuing investigation resulted in incarceration of his wife for both attempted murder by firearm and serial poisoning after soluble barium-containing materials were found hidden in the house.
Discussion
Human barium poisoning is a rarely reported toxic exposure that results in rapid onset of nausea, vomiting, diarrhea, progressive weakness that may end in respiratory paralysis and death if intubation and mechanical ventilation are not promptly initiated. Although the barium found in radiographic contrast media is highly insoluble, ingested barium carbonate and sulfide are rapidly absorbed into the bloodstream, reaching high levels quickly and altering the conductance of potassium channels. The result is erratic variation in blood potassium and prolonged paralysis unless it is immediately suspected and hemodialysis is initiated. In this case, the suspicion level at the time of intubation was insufficient to justify initiating acute hemodialysis.
Soluble barium is available from a number of open sources. Depilatory powders and several rat poisons list barium sulfide or carbonate, both soluble forms of barium rapidly absorbed through the gastrointestinal mucosa, as a major ingredient. One celebrated 2012 case in a city near Chattanooga, Tennessee, involved allegations of barium carbonate poisoning involving rat poison mixed into coffee creamer, but no charges could be filed because the sample handling precluded definitive linkage. Another deliberate toxic poisoning in Texas was traced to soluble barium introduced into a father’s food by his daughter.
The patient reported here experienced 3 years and 19 admissions with 3 episodes of mechanical intubation before his suspected variant HPP was recognized as actually being due to soluble barium poisoning.
Barium does not appear in usual heavy metal urine and blood screens and as a result may not be asked for if not thought of in the differential diagnosis. Physicians dealing with instances of recurrent suspected HPP that do not fit usual age and clinical characteristics for HPP, lack the single-nucleotide polymorphisms associated with the disease, and are not associated with other conditions causing severe hypokalemia, such as renal tubular acidosis, Bartter, Liddle or Gitelman syndrome or severe diuretic or licorice-induced hypokalemia should have soluble barium poisoning included in the differential diagnosis. Appropriately drawn blood specimens in special metal-free sampling tubes and hair barium levels should be included in the diagnostic workup. If poisoning is suspected, a chain of evidence should be obtained to protect possible future criminal investigation against compromise.
Acknowledgments
The authors thanks Tennessee 2nd District Attorney General Barry P. Staubus, 2nd District Assistant Attorney General Teresa A. Nelson, the VA Police Service, and the Tennessee Bureau of Investigation for their help.
1. Ahlawat SK, Sachdev A. Hypokalaemic paralysis. Postgrad Med J. 1999;75(882):193-197.
2. Fontaine B. Periodic paralysis. Adv Genet.2008;63:3-23.
3. Kayal AK, Goswami M, Das M, Jain R. Clinical and biochemical spectrum of hypokalemic paralysis in North: East India. Ann Indian Acad Neurol.2013;16(2):211-217.
4. Johnson CH, VanTassell VJ. Acute barium poisoning with respiratory failure and rhabdomyolysis. Ann Emerg Med. 1991;20(10):1138-1142.
5. Gold R, Reichmann H. Muscle pathology correlates with permanent weakness in hypokalemic periodic paralysis: a case report. Acta Neuropathol. 1992;84(2):202-206.
6. Links TP, Zwarts MJ, Wilmink JT, Molenaar WM, Oosterhuis HJ. Permanent muscle weakness in familial hypokalaemic periodic paralysis. Clinical, radiological and pathological aspects. Brain. 1990;113(pt 6):1873-1889.
7. Tucker C, Villanueva L. Acute hypokalemic periodic paralysis possibly precipitated by albuterol. Am J Health Syst Pharm. 2013;70(18):1588-1591.
8. Liu PY, Jeng CY. Severe hypophosphatemia in a patient with diabetic ketoacidosis and acute respiratory failure. J Chin Med Assoc. 2004;67(7):355-359.
9. Sigue G, Gamble L, Pelitere M, et al. From profound hypokalemia to life-threatening hyperkalemia: a case of barium sulfide poisoning. Arch Intern Med. 2000;160(4):548-541.
10. Kuntzer T, Flocard F, Vial C, et al. Exercise test in muscle channelopathies and other muscle disorders. Muscle Nerve. 2000;23(7):1089-1094.
11. Tengan CH, Antunes AC, Gabbai AA, Manzano GM. The exercise test as a monitor of disease status in hypokalaemic periodic paralysis. J Neurol Neurosurg Psychiatry. 2004;75(3):497-499.
12. McManis PG, Lambert EH, Daube JR. The exercise test in periodic paralysis. Muscle Nerve. 1986;9(8):704-710.
13. Huang K-W. Pa ping (transient paralysis simulating family periodic paralysis). Chin Med J. 1943;61(4):305-312.
14. Ng HY, Lin SH, Hsu CY, Tsai YZ, Chen HC, Lee CT. Hypokalemic paralysis due to Gitelman syndrome:a family study. Neurology. 2006;67(6):1080-1082.
15. Mohta M, Kalra B, Shukla R, Sethi AK. An unusual presentation of hypokalemia. J Anesth Clin Res. 2014;5(3):389.
16. Fujimoto T, Shiiki H, Takahi Y, Dohi K. Primary Sjögren’s Syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest. Clin Rheumatol. 2001;20(5):365-368.
17. Chang YC, Huang CC, Chiou YY, Yu CY. Renal tubular acidosis complicated with hypokalemic periodic paralysis. Pediatr Neurol. 1995;13(1):52-54.
18. Lehmann-Horn F, Jurkat-Rott K, Rüdel R. Periodic paralysis: understanding channelopathies. Curr Neurol Neurosci Rep. 2002;2(1):61-69.
19. Venance SL, Cannon SC, Fialho D, et al; CINCH investigators. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129(pt 1):8-17.
20. Sharma C, Nath K, Parekh J. Reversible electrophysiological abnormalities in hypokalemic paralysis: case report of two cases. Ann Indian Acad Neurol. 2014;17(1):100-102.
21. Sternberg D, Tabti N, Fournier E, Hainque B, Fontaine B. Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. Neurology. 2003;61(6):857-859.
22. Ke Q, Luo B, Qi M, Du Y, Wu W. Gender differences in penetrance and phenotype in hypokalemic periodic paralysis. Muscle Nerve. 2013;47(1):41-45.
23. Griggs RC, Engel WK, Resnick JS. Acetazolamide treatment of hypokalemic periodic paralysis. Prevention of attacks and improvement of persistent weakness. Ann Intern Med. 1970;73(1):39-48.
24. Dalakas MC, Engel WK. Treatment of “permanent” muscle weakness in familial hypokalemic periodic paralysis. Muscle Nerve. 1983;6(3):182-186.
25. Ghose A, Sayeed AA, Hossain A, Rahman R, Faiz A, Haque G. Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series. Cases J. 2009;2:9327.
Hypokalemic periodic paralysis (HPP) is a relatively common and potentially life-threating condition that can be either sporadic or recurring and has both inherited and acquired causes.1 Familial HPP, on the other hand, is a rare condition (1:100,000) caused by loss of function mutations leading to the disruption of membrane potential consequently making them inexcitable.2 Appearance of symptoms is typically in the first or second decade of life (60% of cases have onset aged < 16 years) with susceptible individuals experiencing sudden onset of perioral numbness; weakness; centrifugal paralysis, often with nausea; vomiting and diarrhea; and prostration, usually triggered by highcarbohydrate meals and rest following sustained muscle-group use.3
These symptoms are common to all forms of HPP, making the differential diagnosis wide and confusing. Rhabdomyolysis is occasionally associated with many severe hypokalemic episodes.4 Myopathy and permanent muscle weakness have been reported in HPP.5,6 Other reported inciting factors include a drop in serum potassium caused by β-adrenergic bronchodilator treatment.7 Clinical attacks also have been associated with diabetic ketoacidosis and combined hypokalemia and hypophosphatemia.8 Thyrotoxicosis also causes similar muscle action potential changes but only when hyperthyroidism is uncorrected. 9-12 Less commonly, hypothyroidism has been reported to be associated with hypokalemic paralysis.3
Pa Ping, a condition involving hypokalemic paralysis of uncertain etiology, is geographically centered in the Szechuan region of China.13 Cases of Bartter, Liddle, and Gitelman syndromes also have been associated with hypokalemic paralysis.3,14 There is an association with malignant hyperthermia following or during systemic anesthesia. Patients presenting as Guillain-Barré syndrome have been found to have periodic paralysis triggered by hypokalemia from any cause.15 Sjögren syndrome and renal tubular acidosis also are reported to have triggered symptoms of hypokalemic paralysis.16,17
True type 1 HPP is caused by channelopathies resulting from mutations in the calcium channel gene CACN1AS (HypoPP1), which accounts for 70% of the cases, whereas type 2 HPP is cause by sodium channel gene SCN4A (HypoPP2) mutations, which accounts for 10% to 20% of cases.18,19 An association with a voltage-gated potassium channel KCNE3 mutation has been made but is disputed.20,21 Females typically have less severe and less frequent attacks, and attacks lessen or disappear during pregnancy.22
In a small controlled trial, acetazolamide has been reported to have prophylactic benefit, although a more powerful carbonic anhydrase inhibitor, dichlorophenamide, was reported to be effective in a study after acetazolamide had become ineffective.23,24 These treatments would not be expected to be of clinical use in hypokalemia due to barium poisoning.
Barium poisoning has been reported as a result of accidental contamination of foodstuffs with soluble barium.25 Onset of symptoms is rapid, with nausea, vomiting, diarrhea, and malaise followed rapidly by weakness, which can include the muscles of respiration. This littleconsidered but rapidly lethal poisoning event can be accidental as a result of environmental exposure due to unintentional ingestion of the toxin or deliberate criminal poisoning as in this case. Because deliberate poisoning rarely crosses the mind of the clinician, awareness of the potential similarity of barium poisoning to other forms of HPP and even familial HPP is important.
Case Presentation
A male veteran aged 45 years when treated by the authors was well until moving into a new rural home when he began to experience acute episodes of variable perioral numbness, diarrhea, paresthesias, abdominal cramping, and weakness, which ranged from mild, self-terminating extremity weakness to 3 episodes of respiratory failure that required intubation and mechanical ventilation.
All episodes were accompanied by hypokalemia in the range of 2 to 3 mEq/L, but levels varied erratically during admissions from severe hypokalemia to normo- and hyperkalemia. Over 3 years, the patient was admitted to the hospital 19 times, underwent extensive workup, and was referred to endocrinology services at Duke University, Vanderbilt University, and the Cleveland Clinic. Diagnostic efforts centered on establishing whether he had a latepresenting variant of familial HPP.
Genetic evaluations could not identify known single-nucleotide polymorphisms associated with that condition. The consensus was that he had a potassium leak somewhere between his kidneys and bladder. Recommended management was a high baseline oral potassium supplementation and spironolactone. He had a brief period of improvement after moving to a different house, but the episodes returned once he moved back to his old house despite adherence to recommended treatment. In December 2012, he experienced his worst episode, with potassium 1.8 mEq/L on admission, resulting in admission to the intensive care unit (ICU).
Following a precipitous clinical decline, the patient was intubated and mechanically ventilated. Nephrology was consulted and given the recurrent life-threatening pattern, an intensive chart review was undertaken. It was noted that a urine arsenic level that had been normal several admissions previously at 18 μg/L was elevated during a subsequent admission at 59 μg/L, and several weeks later during a later admission the level had fallen to 15 μg/L. Urine lead was undetectable on 3 occasions, and urine mercury was within normal limits.
Arsenic toxicity did not match the patient’s clinical syndrome, but the pattern seemed to be consistent with the possibility of unexplained toxic exposure and subsequent clearance. Therefore, an intensive literature search for syndromes of environmental exposure or poisoning resembling HPP was undertaken. The search revealed several references in the literature to paralysis similar to HPP that involved ingestion of hair-removing soap and rat poison containing barium sulfide and carbonate. References also pointed to the similarity of the symptoms to Guillain-Barre syndrome.
As a result of that literature search, a blood barium level was collected in the ICU that revealed 14,550 ng/mL. A scalp hair sample showed 6.1 μg barium per gram of hair (reference, 0.53 μg/g to 2 μg/g). Neither the patient nor his wife reported being involved in painting, ceramic work, decorating glassware or fabric with dyes, working with stained glass, smelting, metal welding, or use of vermicides.
A U.S. Environmental Protection Agency team was sent to the house, and a detailed toxic survey of the house and the surrounding grounds was conducted with no excess barium found. Barium levels were checked by a private physician on the wife and 2 minor children. The wife’s barium levels came back undetectable in a blood sample and elevated in a hair sample. One child had a very low detected level in her blood and slightly elevated in her hair, and the other child had a low level in her blood and her hair. Because the circumstances of the wife’s and children’s exposure could not be explained environmentally nor could the veteran’s exposure source be identified, the VA Police Service contacted the Tennessee Bureau of Investigation, and they questioned the veteran and his wife.
Shortly after that the veteran received a paralyzing gunshot wound to the back, and the ensuing investigation resulted in incarceration of his wife for both attempted murder by firearm and serial poisoning after soluble barium-containing materials were found hidden in the house.
Discussion
Human barium poisoning is a rarely reported toxic exposure that results in rapid onset of nausea, vomiting, diarrhea, progressive weakness that may end in respiratory paralysis and death if intubation and mechanical ventilation are not promptly initiated. Although the barium found in radiographic contrast media is highly insoluble, ingested barium carbonate and sulfide are rapidly absorbed into the bloodstream, reaching high levels quickly and altering the conductance of potassium channels. The result is erratic variation in blood potassium and prolonged paralysis unless it is immediately suspected and hemodialysis is initiated. In this case, the suspicion level at the time of intubation was insufficient to justify initiating acute hemodialysis.
Soluble barium is available from a number of open sources. Depilatory powders and several rat poisons list barium sulfide or carbonate, both soluble forms of barium rapidly absorbed through the gastrointestinal mucosa, as a major ingredient. One celebrated 2012 case in a city near Chattanooga, Tennessee, involved allegations of barium carbonate poisoning involving rat poison mixed into coffee creamer, but no charges could be filed because the sample handling precluded definitive linkage. Another deliberate toxic poisoning in Texas was traced to soluble barium introduced into a father’s food by his daughter.
The patient reported here experienced 3 years and 19 admissions with 3 episodes of mechanical intubation before his suspected variant HPP was recognized as actually being due to soluble barium poisoning.
Barium does not appear in usual heavy metal urine and blood screens and as a result may not be asked for if not thought of in the differential diagnosis. Physicians dealing with instances of recurrent suspected HPP that do not fit usual age and clinical characteristics for HPP, lack the single-nucleotide polymorphisms associated with the disease, and are not associated with other conditions causing severe hypokalemia, such as renal tubular acidosis, Bartter, Liddle or Gitelman syndrome or severe diuretic or licorice-induced hypokalemia should have soluble barium poisoning included in the differential diagnosis. Appropriately drawn blood specimens in special metal-free sampling tubes and hair barium levels should be included in the diagnostic workup. If poisoning is suspected, a chain of evidence should be obtained to protect possible future criminal investigation against compromise.
Acknowledgments
The authors thanks Tennessee 2nd District Attorney General Barry P. Staubus, 2nd District Assistant Attorney General Teresa A. Nelson, the VA Police Service, and the Tennessee Bureau of Investigation for their help.
Hypokalemic periodic paralysis (HPP) is a relatively common and potentially life-threating condition that can be either sporadic or recurring and has both inherited and acquired causes.1 Familial HPP, on the other hand, is a rare condition (1:100,000) caused by loss of function mutations leading to the disruption of membrane potential consequently making them inexcitable.2 Appearance of symptoms is typically in the first or second decade of life (60% of cases have onset aged < 16 years) with susceptible individuals experiencing sudden onset of perioral numbness; weakness; centrifugal paralysis, often with nausea; vomiting and diarrhea; and prostration, usually triggered by highcarbohydrate meals and rest following sustained muscle-group use.3
These symptoms are common to all forms of HPP, making the differential diagnosis wide and confusing. Rhabdomyolysis is occasionally associated with many severe hypokalemic episodes.4 Myopathy and permanent muscle weakness have been reported in HPP.5,6 Other reported inciting factors include a drop in serum potassium caused by β-adrenergic bronchodilator treatment.7 Clinical attacks also have been associated with diabetic ketoacidosis and combined hypokalemia and hypophosphatemia.8 Thyrotoxicosis also causes similar muscle action potential changes but only when hyperthyroidism is uncorrected. 9-12 Less commonly, hypothyroidism has been reported to be associated with hypokalemic paralysis.3
Pa Ping, a condition involving hypokalemic paralysis of uncertain etiology, is geographically centered in the Szechuan region of China.13 Cases of Bartter, Liddle, and Gitelman syndromes also have been associated with hypokalemic paralysis.3,14 There is an association with malignant hyperthermia following or during systemic anesthesia. Patients presenting as Guillain-Barré syndrome have been found to have periodic paralysis triggered by hypokalemia from any cause.15 Sjögren syndrome and renal tubular acidosis also are reported to have triggered symptoms of hypokalemic paralysis.16,17
True type 1 HPP is caused by channelopathies resulting from mutations in the calcium channel gene CACN1AS (HypoPP1), which accounts for 70% of the cases, whereas type 2 HPP is cause by sodium channel gene SCN4A (HypoPP2) mutations, which accounts for 10% to 20% of cases.18,19 An association with a voltage-gated potassium channel KCNE3 mutation has been made but is disputed.20,21 Females typically have less severe and less frequent attacks, and attacks lessen or disappear during pregnancy.22
In a small controlled trial, acetazolamide has been reported to have prophylactic benefit, although a more powerful carbonic anhydrase inhibitor, dichlorophenamide, was reported to be effective in a study after acetazolamide had become ineffective.23,24 These treatments would not be expected to be of clinical use in hypokalemia due to barium poisoning.
Barium poisoning has been reported as a result of accidental contamination of foodstuffs with soluble barium.25 Onset of symptoms is rapid, with nausea, vomiting, diarrhea, and malaise followed rapidly by weakness, which can include the muscles of respiration. This littleconsidered but rapidly lethal poisoning event can be accidental as a result of environmental exposure due to unintentional ingestion of the toxin or deliberate criminal poisoning as in this case. Because deliberate poisoning rarely crosses the mind of the clinician, awareness of the potential similarity of barium poisoning to other forms of HPP and even familial HPP is important.
Case Presentation
A male veteran aged 45 years when treated by the authors was well until moving into a new rural home when he began to experience acute episodes of variable perioral numbness, diarrhea, paresthesias, abdominal cramping, and weakness, which ranged from mild, self-terminating extremity weakness to 3 episodes of respiratory failure that required intubation and mechanical ventilation.
All episodes were accompanied by hypokalemia in the range of 2 to 3 mEq/L, but levels varied erratically during admissions from severe hypokalemia to normo- and hyperkalemia. Over 3 years, the patient was admitted to the hospital 19 times, underwent extensive workup, and was referred to endocrinology services at Duke University, Vanderbilt University, and the Cleveland Clinic. Diagnostic efforts centered on establishing whether he had a latepresenting variant of familial HPP.
Genetic evaluations could not identify known single-nucleotide polymorphisms associated with that condition. The consensus was that he had a potassium leak somewhere between his kidneys and bladder. Recommended management was a high baseline oral potassium supplementation and spironolactone. He had a brief period of improvement after moving to a different house, but the episodes returned once he moved back to his old house despite adherence to recommended treatment. In December 2012, he experienced his worst episode, with potassium 1.8 mEq/L on admission, resulting in admission to the intensive care unit (ICU).
Following a precipitous clinical decline, the patient was intubated and mechanically ventilated. Nephrology was consulted and given the recurrent life-threatening pattern, an intensive chart review was undertaken. It was noted that a urine arsenic level that had been normal several admissions previously at 18 μg/L was elevated during a subsequent admission at 59 μg/L, and several weeks later during a later admission the level had fallen to 15 μg/L. Urine lead was undetectable on 3 occasions, and urine mercury was within normal limits.
Arsenic toxicity did not match the patient’s clinical syndrome, but the pattern seemed to be consistent with the possibility of unexplained toxic exposure and subsequent clearance. Therefore, an intensive literature search for syndromes of environmental exposure or poisoning resembling HPP was undertaken. The search revealed several references in the literature to paralysis similar to HPP that involved ingestion of hair-removing soap and rat poison containing barium sulfide and carbonate. References also pointed to the similarity of the symptoms to Guillain-Barre syndrome.
As a result of that literature search, a blood barium level was collected in the ICU that revealed 14,550 ng/mL. A scalp hair sample showed 6.1 μg barium per gram of hair (reference, 0.53 μg/g to 2 μg/g). Neither the patient nor his wife reported being involved in painting, ceramic work, decorating glassware or fabric with dyes, working with stained glass, smelting, metal welding, or use of vermicides.
A U.S. Environmental Protection Agency team was sent to the house, and a detailed toxic survey of the house and the surrounding grounds was conducted with no excess barium found. Barium levels were checked by a private physician on the wife and 2 minor children. The wife’s barium levels came back undetectable in a blood sample and elevated in a hair sample. One child had a very low detected level in her blood and slightly elevated in her hair, and the other child had a low level in her blood and her hair. Because the circumstances of the wife’s and children’s exposure could not be explained environmentally nor could the veteran’s exposure source be identified, the VA Police Service contacted the Tennessee Bureau of Investigation, and they questioned the veteran and his wife.
Shortly after that the veteran received a paralyzing gunshot wound to the back, and the ensuing investigation resulted in incarceration of his wife for both attempted murder by firearm and serial poisoning after soluble barium-containing materials were found hidden in the house.
Discussion
Human barium poisoning is a rarely reported toxic exposure that results in rapid onset of nausea, vomiting, diarrhea, progressive weakness that may end in respiratory paralysis and death if intubation and mechanical ventilation are not promptly initiated. Although the barium found in radiographic contrast media is highly insoluble, ingested barium carbonate and sulfide are rapidly absorbed into the bloodstream, reaching high levels quickly and altering the conductance of potassium channels. The result is erratic variation in blood potassium and prolonged paralysis unless it is immediately suspected and hemodialysis is initiated. In this case, the suspicion level at the time of intubation was insufficient to justify initiating acute hemodialysis.
Soluble barium is available from a number of open sources. Depilatory powders and several rat poisons list barium sulfide or carbonate, both soluble forms of barium rapidly absorbed through the gastrointestinal mucosa, as a major ingredient. One celebrated 2012 case in a city near Chattanooga, Tennessee, involved allegations of barium carbonate poisoning involving rat poison mixed into coffee creamer, but no charges could be filed because the sample handling precluded definitive linkage. Another deliberate toxic poisoning in Texas was traced to soluble barium introduced into a father’s food by his daughter.
The patient reported here experienced 3 years and 19 admissions with 3 episodes of mechanical intubation before his suspected variant HPP was recognized as actually being due to soluble barium poisoning.
Barium does not appear in usual heavy metal urine and blood screens and as a result may not be asked for if not thought of in the differential diagnosis. Physicians dealing with instances of recurrent suspected HPP that do not fit usual age and clinical characteristics for HPP, lack the single-nucleotide polymorphisms associated with the disease, and are not associated with other conditions causing severe hypokalemia, such as renal tubular acidosis, Bartter, Liddle or Gitelman syndrome or severe diuretic or licorice-induced hypokalemia should have soluble barium poisoning included in the differential diagnosis. Appropriately drawn blood specimens in special metal-free sampling tubes and hair barium levels should be included in the diagnostic workup. If poisoning is suspected, a chain of evidence should be obtained to protect possible future criminal investigation against compromise.
Acknowledgments
The authors thanks Tennessee 2nd District Attorney General Barry P. Staubus, 2nd District Assistant Attorney General Teresa A. Nelson, the VA Police Service, and the Tennessee Bureau of Investigation for their help.
1. Ahlawat SK, Sachdev A. Hypokalaemic paralysis. Postgrad Med J. 1999;75(882):193-197.
2. Fontaine B. Periodic paralysis. Adv Genet.2008;63:3-23.
3. Kayal AK, Goswami M, Das M, Jain R. Clinical and biochemical spectrum of hypokalemic paralysis in North: East India. Ann Indian Acad Neurol.2013;16(2):211-217.
4. Johnson CH, VanTassell VJ. Acute barium poisoning with respiratory failure and rhabdomyolysis. Ann Emerg Med. 1991;20(10):1138-1142.
5. Gold R, Reichmann H. Muscle pathology correlates with permanent weakness in hypokalemic periodic paralysis: a case report. Acta Neuropathol. 1992;84(2):202-206.
6. Links TP, Zwarts MJ, Wilmink JT, Molenaar WM, Oosterhuis HJ. Permanent muscle weakness in familial hypokalaemic periodic paralysis. Clinical, radiological and pathological aspects. Brain. 1990;113(pt 6):1873-1889.
7. Tucker C, Villanueva L. Acute hypokalemic periodic paralysis possibly precipitated by albuterol. Am J Health Syst Pharm. 2013;70(18):1588-1591.
8. Liu PY, Jeng CY. Severe hypophosphatemia in a patient with diabetic ketoacidosis and acute respiratory failure. J Chin Med Assoc. 2004;67(7):355-359.
9. Sigue G, Gamble L, Pelitere M, et al. From profound hypokalemia to life-threatening hyperkalemia: a case of barium sulfide poisoning. Arch Intern Med. 2000;160(4):548-541.
10. Kuntzer T, Flocard F, Vial C, et al. Exercise test in muscle channelopathies and other muscle disorders. Muscle Nerve. 2000;23(7):1089-1094.
11. Tengan CH, Antunes AC, Gabbai AA, Manzano GM. The exercise test as a monitor of disease status in hypokalaemic periodic paralysis. J Neurol Neurosurg Psychiatry. 2004;75(3):497-499.
12. McManis PG, Lambert EH, Daube JR. The exercise test in periodic paralysis. Muscle Nerve. 1986;9(8):704-710.
13. Huang K-W. Pa ping (transient paralysis simulating family periodic paralysis). Chin Med J. 1943;61(4):305-312.
14. Ng HY, Lin SH, Hsu CY, Tsai YZ, Chen HC, Lee CT. Hypokalemic paralysis due to Gitelman syndrome:a family study. Neurology. 2006;67(6):1080-1082.
15. Mohta M, Kalra B, Shukla R, Sethi AK. An unusual presentation of hypokalemia. J Anesth Clin Res. 2014;5(3):389.
16. Fujimoto T, Shiiki H, Takahi Y, Dohi K. Primary Sjögren’s Syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest. Clin Rheumatol. 2001;20(5):365-368.
17. Chang YC, Huang CC, Chiou YY, Yu CY. Renal tubular acidosis complicated with hypokalemic periodic paralysis. Pediatr Neurol. 1995;13(1):52-54.
18. Lehmann-Horn F, Jurkat-Rott K, Rüdel R. Periodic paralysis: understanding channelopathies. Curr Neurol Neurosci Rep. 2002;2(1):61-69.
19. Venance SL, Cannon SC, Fialho D, et al; CINCH investigators. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129(pt 1):8-17.
20. Sharma C, Nath K, Parekh J. Reversible electrophysiological abnormalities in hypokalemic paralysis: case report of two cases. Ann Indian Acad Neurol. 2014;17(1):100-102.
21. Sternberg D, Tabti N, Fournier E, Hainque B, Fontaine B. Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. Neurology. 2003;61(6):857-859.
22. Ke Q, Luo B, Qi M, Du Y, Wu W. Gender differences in penetrance and phenotype in hypokalemic periodic paralysis. Muscle Nerve. 2013;47(1):41-45.
23. Griggs RC, Engel WK, Resnick JS. Acetazolamide treatment of hypokalemic periodic paralysis. Prevention of attacks and improvement of persistent weakness. Ann Intern Med. 1970;73(1):39-48.
24. Dalakas MC, Engel WK. Treatment of “permanent” muscle weakness in familial hypokalemic periodic paralysis. Muscle Nerve. 1983;6(3):182-186.
25. Ghose A, Sayeed AA, Hossain A, Rahman R, Faiz A, Haque G. Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series. Cases J. 2009;2:9327.
1. Ahlawat SK, Sachdev A. Hypokalaemic paralysis. Postgrad Med J. 1999;75(882):193-197.
2. Fontaine B. Periodic paralysis. Adv Genet.2008;63:3-23.
3. Kayal AK, Goswami M, Das M, Jain R. Clinical and biochemical spectrum of hypokalemic paralysis in North: East India. Ann Indian Acad Neurol.2013;16(2):211-217.
4. Johnson CH, VanTassell VJ. Acute barium poisoning with respiratory failure and rhabdomyolysis. Ann Emerg Med. 1991;20(10):1138-1142.
5. Gold R, Reichmann H. Muscle pathology correlates with permanent weakness in hypokalemic periodic paralysis: a case report. Acta Neuropathol. 1992;84(2):202-206.
6. Links TP, Zwarts MJ, Wilmink JT, Molenaar WM, Oosterhuis HJ. Permanent muscle weakness in familial hypokalaemic periodic paralysis. Clinical, radiological and pathological aspects. Brain. 1990;113(pt 6):1873-1889.
7. Tucker C, Villanueva L. Acute hypokalemic periodic paralysis possibly precipitated by albuterol. Am J Health Syst Pharm. 2013;70(18):1588-1591.
8. Liu PY, Jeng CY. Severe hypophosphatemia in a patient with diabetic ketoacidosis and acute respiratory failure. J Chin Med Assoc. 2004;67(7):355-359.
9. Sigue G, Gamble L, Pelitere M, et al. From profound hypokalemia to life-threatening hyperkalemia: a case of barium sulfide poisoning. Arch Intern Med. 2000;160(4):548-541.
10. Kuntzer T, Flocard F, Vial C, et al. Exercise test in muscle channelopathies and other muscle disorders. Muscle Nerve. 2000;23(7):1089-1094.
11. Tengan CH, Antunes AC, Gabbai AA, Manzano GM. The exercise test as a monitor of disease status in hypokalaemic periodic paralysis. J Neurol Neurosurg Psychiatry. 2004;75(3):497-499.
12. McManis PG, Lambert EH, Daube JR. The exercise test in periodic paralysis. Muscle Nerve. 1986;9(8):704-710.
13. Huang K-W. Pa ping (transient paralysis simulating family periodic paralysis). Chin Med J. 1943;61(4):305-312.
14. Ng HY, Lin SH, Hsu CY, Tsai YZ, Chen HC, Lee CT. Hypokalemic paralysis due to Gitelman syndrome:a family study. Neurology. 2006;67(6):1080-1082.
15. Mohta M, Kalra B, Shukla R, Sethi AK. An unusual presentation of hypokalemia. J Anesth Clin Res. 2014;5(3):389.
16. Fujimoto T, Shiiki H, Takahi Y, Dohi K. Primary Sjögren’s Syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest. Clin Rheumatol. 2001;20(5):365-368.
17. Chang YC, Huang CC, Chiou YY, Yu CY. Renal tubular acidosis complicated with hypokalemic periodic paralysis. Pediatr Neurol. 1995;13(1):52-54.
18. Lehmann-Horn F, Jurkat-Rott K, Rüdel R. Periodic paralysis: understanding channelopathies. Curr Neurol Neurosci Rep. 2002;2(1):61-69.
19. Venance SL, Cannon SC, Fialho D, et al; CINCH investigators. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain. 2006;129(pt 1):8-17.
20. Sharma C, Nath K, Parekh J. Reversible electrophysiological abnormalities in hypokalemic paralysis: case report of two cases. Ann Indian Acad Neurol. 2014;17(1):100-102.
21. Sternberg D, Tabti N, Fournier E, Hainque B, Fontaine B. Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. Neurology. 2003;61(6):857-859.
22. Ke Q, Luo B, Qi M, Du Y, Wu W. Gender differences in penetrance and phenotype in hypokalemic periodic paralysis. Muscle Nerve. 2013;47(1):41-45.
23. Griggs RC, Engel WK, Resnick JS. Acetazolamide treatment of hypokalemic periodic paralysis. Prevention of attacks and improvement of persistent weakness. Ann Intern Med. 1970;73(1):39-48.
24. Dalakas MC, Engel WK. Treatment of “permanent” muscle weakness in familial hypokalemic periodic paralysis. Muscle Nerve. 1983;6(3):182-186.
25. Ghose A, Sayeed AA, Hossain A, Rahman R, Faiz A, Haque G. Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series. Cases J. 2009;2:9327.
Federal Health Care Data Trends 2017 Introduction
Military service comes with many health care costs, both immediate and long term. These costs are incurred by active-duty and veteran patients, as well as the VA and DoD systems that have struggled to adequately meet their health care needs. The VA and DoD health care systems face a myriad of challenges in treating their diverse populations.
Identifying and responding to health care challenges requires reliable and detailed data. The 2017 Federal Health Care Data Trends was developed not only to report important data on the most significant health care challenges in federal medicine, but also to simplify and identify emergent trends.
The men and women who serve in the U.S. military are more likely to be diagnosed with posttraumatic stress disorder, diabetes mellitus, and chronic obstructive pulmonary disease. Agent Orange, burn pits, and other toxic exposures also increase their risk of developing multiple types of cancer, multiple sclerosis, asthma, and many other conditions. Veterans are likely to be older than nonveterans (the median age of male veterans is 64 years, compared with 41 years for nonveterans), and therefore at risk for age-related conditions.
Of the nearly 22 million veterans in the U.S., 8.9 million are enrolled in the VA, and just short of 6 million access health care services annually. Active-duty service members make up just 15% of the military health system, while the family members of active-duty service members, National Guard members, reservists, and retirees constitute more than half of the TRICARE population.
Click here to continue reading.
Military service comes with many health care costs, both immediate and long term. These costs are incurred by active-duty and veteran patients, as well as the VA and DoD systems that have struggled to adequately meet their health care needs. The VA and DoD health care systems face a myriad of challenges in treating their diverse populations.
Identifying and responding to health care challenges requires reliable and detailed data. The 2017 Federal Health Care Data Trends was developed not only to report important data on the most significant health care challenges in federal medicine, but also to simplify and identify emergent trends.
The men and women who serve in the U.S. military are more likely to be diagnosed with posttraumatic stress disorder, diabetes mellitus, and chronic obstructive pulmonary disease. Agent Orange, burn pits, and other toxic exposures also increase their risk of developing multiple types of cancer, multiple sclerosis, asthma, and many other conditions. Veterans are likely to be older than nonveterans (the median age of male veterans is 64 years, compared with 41 years for nonveterans), and therefore at risk for age-related conditions.
Of the nearly 22 million veterans in the U.S., 8.9 million are enrolled in the VA, and just short of 6 million access health care services annually. Active-duty service members make up just 15% of the military health system, while the family members of active-duty service members, National Guard members, reservists, and retirees constitute more than half of the TRICARE population.
Click here to continue reading.
Military service comes with many health care costs, both immediate and long term. These costs are incurred by active-duty and veteran patients, as well as the VA and DoD systems that have struggled to adequately meet their health care needs. The VA and DoD health care systems face a myriad of challenges in treating their diverse populations.
Identifying and responding to health care challenges requires reliable and detailed data. The 2017 Federal Health Care Data Trends was developed not only to report important data on the most significant health care challenges in federal medicine, but also to simplify and identify emergent trends.
The men and women who serve in the U.S. military are more likely to be diagnosed with posttraumatic stress disorder, diabetes mellitus, and chronic obstructive pulmonary disease. Agent Orange, burn pits, and other toxic exposures also increase their risk of developing multiple types of cancer, multiple sclerosis, asthma, and many other conditions. Veterans are likely to be older than nonveterans (the median age of male veterans is 64 years, compared with 41 years for nonveterans), and therefore at risk for age-related conditions.
Of the nearly 22 million veterans in the U.S., 8.9 million are enrolled in the VA, and just short of 6 million access health care services annually. Active-duty service members make up just 15% of the military health system, while the family members of active-duty service members, National Guard members, reservists, and retirees constitute more than half of the TRICARE population.
Click here to continue reading.
Studies support testing for iron deficiency in young women
A pair of studies suggest physicians should consider testing female adolescents for iron deficiency within a few years of starting menses.
Women are typically tested for anemia in their teens, with a quick and affordable hemoglobin test.
However, iron deficiency can develop years before anemia and can be missed by hemoglobin testing alone.
Blood tests for iron deficiency without anemia are more costly and more difficult to obtain than hemoglobin testing for anemia.
Deepa Sekhar, MD, of Penn State College of Medicine in Hershey, Pennsylvania, and her colleagues set out to determine risk factors for iron deficiency without anemia in order to pinpoint which women could benefit most from the more costly testing.
The results of the researchers’ 2 studies were published in PLOS ONE and The Journal of Pediatrics.
PLOS ONE study
The researchers evaluated data from 6216 females, ages 12 to 49, who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. As part of the survey, participants were tested for both iron deficiency and anemia.
Eight percent of all subjects (n=494) had iron deficiency.
Nine percent (n=250) of non-anemic younger women (ages 12-21) had iron deficiency, as did 7% (n=244) of older women (ages 22-49) who were not anemic.
The researchers looked at potential risk factors for iron deficiency, including the age when women started menstruating, as well as their race/ethnicity, poverty status, food insecurity, tobacco or nicotine use, dietary information, body mass index, and physical activity.
All of these factors have been associated with iron-deficiency anemia in women in prior studies.
In this study, there was only 1 risk factor significantly associated with iron deficiency without anemia.
Young women (ages 12-21) who had been menstruating for more than 3 years had a significantly higher risk of iron deficiency without anemia (risk ratio=3.18).
The Journal of Pediatrics study
In this study, the researchers looked at whether a questionnaire could better predict iron status.
The questionnaire included questions on depression, poor attention, and daytime sleepiness, all of which have been associated with iron deficiency or iron-deficiency anemia, but were not captured in the prior NHANES analyses.
This questionnaire was compared to the 4 questions assessing iron-deficiency anemia risk in the Bright Futures Adolescent Previsit Questionnaire, a survey recommended for physician use by the American Academy of Pediatrics.
Ninety-six female adolescents participated in this study. Eighteen percent of them (n=17) had iron deficiency, and 5% (n=5) had iron-deficiency anemia.
Both the Bright Futures questions and the researchers’ risk assessment questionnaire poorly predicted ferritin and hemoglobin values in these subjects.
Mean differences in depression, poor attention, food insecurity, daytime sleepiness, and body mass index percentile were not significantly associated with ferritin or hemoglobin.
Conclusions
The results of these 2 studies suggest that risk factors and assessments cannot accurately determine which young women should receive testing for iron deficiency, although results from the first study might be used to determine when testing should occur.
“I think we need to establish the optimal timing for an objective assessment of adolescent iron deficiency and anemia,” Dr Sekhar said.
She believes the appropriate age may be 16 years old, when most females will have been menstruating for at least 3 years.
Further research will be needed to determine which blood test for iron deficiency without anemia is accurate, cost-efficient, and practical for routine doctor’s office use.
This test should be given with hemoglobin testing to catch all young women on the spectrum of iron deficiency, Dr Sekhar said. 
A pair of studies suggest physicians should consider testing female adolescents for iron deficiency within a few years of starting menses.
Women are typically tested for anemia in their teens, with a quick and affordable hemoglobin test.
However, iron deficiency can develop years before anemia and can be missed by hemoglobin testing alone.
Blood tests for iron deficiency without anemia are more costly and more difficult to obtain than hemoglobin testing for anemia.
Deepa Sekhar, MD, of Penn State College of Medicine in Hershey, Pennsylvania, and her colleagues set out to determine risk factors for iron deficiency without anemia in order to pinpoint which women could benefit most from the more costly testing.
The results of the researchers’ 2 studies were published in PLOS ONE and The Journal of Pediatrics.
PLOS ONE study
The researchers evaluated data from 6216 females, ages 12 to 49, who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. As part of the survey, participants were tested for both iron deficiency and anemia.
Eight percent of all subjects (n=494) had iron deficiency.
Nine percent (n=250) of non-anemic younger women (ages 12-21) had iron deficiency, as did 7% (n=244) of older women (ages 22-49) who were not anemic.
The researchers looked at potential risk factors for iron deficiency, including the age when women started menstruating, as well as their race/ethnicity, poverty status, food insecurity, tobacco or nicotine use, dietary information, body mass index, and physical activity.
All of these factors have been associated with iron-deficiency anemia in women in prior studies.
In this study, there was only 1 risk factor significantly associated with iron deficiency without anemia.
Young women (ages 12-21) who had been menstruating for more than 3 years had a significantly higher risk of iron deficiency without anemia (risk ratio=3.18).
The Journal of Pediatrics study
In this study, the researchers looked at whether a questionnaire could better predict iron status.
The questionnaire included questions on depression, poor attention, and daytime sleepiness, all of which have been associated with iron deficiency or iron-deficiency anemia, but were not captured in the prior NHANES analyses.
This questionnaire was compared to the 4 questions assessing iron-deficiency anemia risk in the Bright Futures Adolescent Previsit Questionnaire, a survey recommended for physician use by the American Academy of Pediatrics.
Ninety-six female adolescents participated in this study. Eighteen percent of them (n=17) had iron deficiency, and 5% (n=5) had iron-deficiency anemia.
Both the Bright Futures questions and the researchers’ risk assessment questionnaire poorly predicted ferritin and hemoglobin values in these subjects.
Mean differences in depression, poor attention, food insecurity, daytime sleepiness, and body mass index percentile were not significantly associated with ferritin or hemoglobin.
Conclusions
The results of these 2 studies suggest that risk factors and assessments cannot accurately determine which young women should receive testing for iron deficiency, although results from the first study might be used to determine when testing should occur.
“I think we need to establish the optimal timing for an objective assessment of adolescent iron deficiency and anemia,” Dr Sekhar said.
She believes the appropriate age may be 16 years old, when most females will have been menstruating for at least 3 years.
Further research will be needed to determine which blood test for iron deficiency without anemia is accurate, cost-efficient, and practical for routine doctor’s office use.
This test should be given with hemoglobin testing to catch all young women on the spectrum of iron deficiency, Dr Sekhar said.
A pair of studies suggest physicians should consider testing female adolescents for iron deficiency within a few years of starting menses.
Women are typically tested for anemia in their teens, with a quick and affordable hemoglobin test.
However, iron deficiency can develop years before anemia and can be missed by hemoglobin testing alone.
Blood tests for iron deficiency without anemia are more costly and more difficult to obtain than hemoglobin testing for anemia.
Deepa Sekhar, MD, of Penn State College of Medicine in Hershey, Pennsylvania, and her colleagues set out to determine risk factors for iron deficiency without anemia in order to pinpoint which women could benefit most from the more costly testing.
The results of the researchers’ 2 studies were published in PLOS ONE and The Journal of Pediatrics.
PLOS ONE study
The researchers evaluated data from 6216 females, ages 12 to 49, who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. As part of the survey, participants were tested for both iron deficiency and anemia.
Eight percent of all subjects (n=494) had iron deficiency.
Nine percent (n=250) of non-anemic younger women (ages 12-21) had iron deficiency, as did 7% (n=244) of older women (ages 22-49) who were not anemic.
The researchers looked at potential risk factors for iron deficiency, including the age when women started menstruating, as well as their race/ethnicity, poverty status, food insecurity, tobacco or nicotine use, dietary information, body mass index, and physical activity.
All of these factors have been associated with iron-deficiency anemia in women in prior studies.
In this study, there was only 1 risk factor significantly associated with iron deficiency without anemia.
Young women (ages 12-21) who had been menstruating for more than 3 years had a significantly higher risk of iron deficiency without anemia (risk ratio=3.18).
The Journal of Pediatrics study
In this study, the researchers looked at whether a questionnaire could better predict iron status.
The questionnaire included questions on depression, poor attention, and daytime sleepiness, all of which have been associated with iron deficiency or iron-deficiency anemia, but were not captured in the prior NHANES analyses.
This questionnaire was compared to the 4 questions assessing iron-deficiency anemia risk in the Bright Futures Adolescent Previsit Questionnaire, a survey recommended for physician use by the American Academy of Pediatrics.
Ninety-six female adolescents participated in this study. Eighteen percent of them (n=17) had iron deficiency, and 5% (n=5) had iron-deficiency anemia.
Both the Bright Futures questions and the researchers’ risk assessment questionnaire poorly predicted ferritin and hemoglobin values in these subjects.
Mean differences in depression, poor attention, food insecurity, daytime sleepiness, and body mass index percentile were not significantly associated with ferritin or hemoglobin.
Conclusions
The results of these 2 studies suggest that risk factors and assessments cannot accurately determine which young women should receive testing for iron deficiency, although results from the first study might be used to determine when testing should occur.
“I think we need to establish the optimal timing for an objective assessment of adolescent iron deficiency and anemia,” Dr Sekhar said.
She believes the appropriate age may be 16 years old, when most females will have been menstruating for at least 3 years.
Further research will be needed to determine which blood test for iron deficiency without anemia is accurate, cost-efficient, and practical for routine doctor’s office use.
This test should be given with hemoglobin testing to catch all young women on the spectrum of iron deficiency, Dr Sekhar said.