Heidi Splete

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Through the AGA Center for Gut Microbiome Research and Education, AGA is committed to keeping you up-to-speed on the latest news, research and policy updates related to the gut microbiome: www.gastro.org/microbiome. 

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Through the AGA Center for Gut Microbiome Research and Education, AGA is committed to keeping you up-to-speed on the latest news, research and policy updates related to the gut microbiome: www.gastro.org/microbiome. 

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Through the AGA Center for Gut Microbiome Research and Education, AGA is committed to keeping you up-to-speed on the latest news, research and policy updates related to the gut microbiome: www.gastro.org/microbiome. 

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

The proportion of U.S. children who are underinsured for health care increased by 3.4% from 2016 to 2019, reflecting approximately 2.4 million underinsured children, based on data from the National Survey of Children’s Health.

Children with inconsistent or inadequate medical coverage are more likely to forgo medical care, including preventive well-child visits, and to have unmet medical needs such as prescription medications, Justin Yu, MD, of the Children’s Hospital of Pittsburgh, and colleagues wrote. Although the American Academy of Pediatrics and the Healthy People 2030 guidelines have endorsed increasing the proportion of children with adequate coverage, recent studies suggest that advances in insuring children in the wake of the Affordable Care Act have stalled, and trends in child insurance have not been well described, the researchers said.

In a study published in Pediatrics, the researchers reviewed data from the combined 2016-2019 datasets of the National Survey of Children’s Health, a survey funded by the Maternal and Child Health Bureau of the Health Resources and Services Administration.

Adequate insurance was defined as a composite with three questions; whether the benefits “usually” or “always” meet the child’s needs; the benefits “usually” or “always” allow the child to see needed providers; and whether out-of-pocket expenses are either absent or “usually” or “always” reasonable.

Overall, the proportion of children with underinsurance increased from 30.6% in 2016 to 34.0% in 2019.

Underinsurance was significantly associated with increased health complexity and private insurance, with adjusted odds ratios of 1.9 and 3.5, respectively. In addition, underinsurance was significantly associated with child age of 6 years or older, non-Black racial identity, U.S. nonnative status, and a family income of at least 100% above the Federal Poverty Level. Notably, underinsurance grew significantly among White children living in “middle-income” families, the researchers said.

The increase in underinsurance was driven primarily by increased insurance inadequacy, which rose from 24.8% to 27.9% over the study period. The increase in insurance inadequacy was described primarily as unreasonable out-of-pocket medical expenses, according to the survey respondents.

The study findings were limited by several factors including the inability to show causality or to describe changes in outcomes for individual children, the researchers noted. Other limitations include the reliance on parent reports and the lack of a definitive definition of underinsurance.

However, the results highlight the ongoing problem of underinsurance in children, and the need to address the factors that contribute to inadequate insurance for children, the researchers said.

“Our data, demonstrating a shift from public to private insurance that is more likely to be inadequate, in conjunction with existing literature linking Medicaid/CHIP [Children’s Health Insurance Program] coverage with improved access to medical care as well as improved long-term outcomes in adulthood, should give policy makers and payers pause as they contemplate strategies to improve child health,” they concluded.

Nationwide action needed to fight underinsurance

The authors should be commended for highlighting the disturbing trend in underinsurance among children in the United States, Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, said in an interview.

“With the passage of the Affordable Care Act, the population of uninsured and underinsured had shrunk quite a bit, but in the past few years, the numbers are growing again. This population has often been called the working poor; the vast majority are legal residents who make too much to qualify for Medicaid/CHIP programs, and whose employers don’t offer affordable robust health care coverage,” Dr. Joos said.

“These families have to make the risky decisions of how much of the family budget to spend on insurance plans, often to the detriment of their own and their children’s health,” he explained. “If you believe the old adage about ‘an ounce of prevention,’ then the money we spend on preserving the health of our children will more than pay for itself in benefits of increased productivity and health care savings in the 1-2 decades later when they reach adulthood. It is time for us as a nation to come up with a more comprehensive baseline coverage for all pediatric patients and take away any barriers for families to access basic health care for children.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

The proportion of U.S. children who are underinsured for health care increased by 3.4% from 2016 to 2019, reflecting approximately 2.4 million underinsured children, based on data from the National Survey of Children’s Health.

Children with inconsistent or inadequate medical coverage are more likely to forgo medical care, including preventive well-child visits, and to have unmet medical needs such as prescription medications, Justin Yu, MD, of the Children’s Hospital of Pittsburgh, and colleagues wrote. Although the American Academy of Pediatrics and the Healthy People 2030 guidelines have endorsed increasing the proportion of children with adequate coverage, recent studies suggest that advances in insuring children in the wake of the Affordable Care Act have stalled, and trends in child insurance have not been well described, the researchers said.

In a study published in Pediatrics, the researchers reviewed data from the combined 2016-2019 datasets of the National Survey of Children’s Health, a survey funded by the Maternal and Child Health Bureau of the Health Resources and Services Administration.

Adequate insurance was defined as a composite with three questions; whether the benefits “usually” or “always” meet the child’s needs; the benefits “usually” or “always” allow the child to see needed providers; and whether out-of-pocket expenses are either absent or “usually” or “always” reasonable.

Overall, the proportion of children with underinsurance increased from 30.6% in 2016 to 34.0% in 2019.

Underinsurance was significantly associated with increased health complexity and private insurance, with adjusted odds ratios of 1.9 and 3.5, respectively. In addition, underinsurance was significantly associated with child age of 6 years or older, non-Black racial identity, U.S. nonnative status, and a family income of at least 100% above the Federal Poverty Level. Notably, underinsurance grew significantly among White children living in “middle-income” families, the researchers said.

The increase in underinsurance was driven primarily by increased insurance inadequacy, which rose from 24.8% to 27.9% over the study period. The increase in insurance inadequacy was described primarily as unreasonable out-of-pocket medical expenses, according to the survey respondents.

The study findings were limited by several factors including the inability to show causality or to describe changes in outcomes for individual children, the researchers noted. Other limitations include the reliance on parent reports and the lack of a definitive definition of underinsurance.

However, the results highlight the ongoing problem of underinsurance in children, and the need to address the factors that contribute to inadequate insurance for children, the researchers said.

“Our data, demonstrating a shift from public to private insurance that is more likely to be inadequate, in conjunction with existing literature linking Medicaid/CHIP [Children’s Health Insurance Program] coverage with improved access to medical care as well as improved long-term outcomes in adulthood, should give policy makers and payers pause as they contemplate strategies to improve child health,” they concluded.

Nationwide action needed to fight underinsurance

The authors should be commended for highlighting the disturbing trend in underinsurance among children in the United States, Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, said in an interview.

“With the passage of the Affordable Care Act, the population of uninsured and underinsured had shrunk quite a bit, but in the past few years, the numbers are growing again. This population has often been called the working poor; the vast majority are legal residents who make too much to qualify for Medicaid/CHIP programs, and whose employers don’t offer affordable robust health care coverage,” Dr. Joos said.

“These families have to make the risky decisions of how much of the family budget to spend on insurance plans, often to the detriment of their own and their children’s health,” he explained. “If you believe the old adage about ‘an ounce of prevention,’ then the money we spend on preserving the health of our children will more than pay for itself in benefits of increased productivity and health care savings in the 1-2 decades later when they reach adulthood. It is time for us as a nation to come up with a more comprehensive baseline coverage for all pediatric patients and take away any barriers for families to access basic health care for children.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

The proportion of U.S. children who are underinsured for health care increased by 3.4% from 2016 to 2019, reflecting approximately 2.4 million underinsured children, based on data from the National Survey of Children’s Health.

Children with inconsistent or inadequate medical coverage are more likely to forgo medical care, including preventive well-child visits, and to have unmet medical needs such as prescription medications, Justin Yu, MD, of the Children’s Hospital of Pittsburgh, and colleagues wrote. Although the American Academy of Pediatrics and the Healthy People 2030 guidelines have endorsed increasing the proportion of children with adequate coverage, recent studies suggest that advances in insuring children in the wake of the Affordable Care Act have stalled, and trends in child insurance have not been well described, the researchers said.

In a study published in Pediatrics, the researchers reviewed data from the combined 2016-2019 datasets of the National Survey of Children’s Health, a survey funded by the Maternal and Child Health Bureau of the Health Resources and Services Administration.

Adequate insurance was defined as a composite with three questions; whether the benefits “usually” or “always” meet the child’s needs; the benefits “usually” or “always” allow the child to see needed providers; and whether out-of-pocket expenses are either absent or “usually” or “always” reasonable.

Overall, the proportion of children with underinsurance increased from 30.6% in 2016 to 34.0% in 2019.

Underinsurance was significantly associated with increased health complexity and private insurance, with adjusted odds ratios of 1.9 and 3.5, respectively. In addition, underinsurance was significantly associated with child age of 6 years or older, non-Black racial identity, U.S. nonnative status, and a family income of at least 100% above the Federal Poverty Level. Notably, underinsurance grew significantly among White children living in “middle-income” families, the researchers said.

The increase in underinsurance was driven primarily by increased insurance inadequacy, which rose from 24.8% to 27.9% over the study period. The increase in insurance inadequacy was described primarily as unreasonable out-of-pocket medical expenses, according to the survey respondents.

The study findings were limited by several factors including the inability to show causality or to describe changes in outcomes for individual children, the researchers noted. Other limitations include the reliance on parent reports and the lack of a definitive definition of underinsurance.

However, the results highlight the ongoing problem of underinsurance in children, and the need to address the factors that contribute to inadequate insurance for children, the researchers said.

“Our data, demonstrating a shift from public to private insurance that is more likely to be inadequate, in conjunction with existing literature linking Medicaid/CHIP [Children’s Health Insurance Program] coverage with improved access to medical care as well as improved long-term outcomes in adulthood, should give policy makers and payers pause as they contemplate strategies to improve child health,” they concluded.

Nationwide action needed to fight underinsurance

The authors should be commended for highlighting the disturbing trend in underinsurance among children in the United States, Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, said in an interview.

“With the passage of the Affordable Care Act, the population of uninsured and underinsured had shrunk quite a bit, but in the past few years, the numbers are growing again. This population has often been called the working poor; the vast majority are legal residents who make too much to qualify for Medicaid/CHIP programs, and whose employers don’t offer affordable robust health care coverage,” Dr. Joos said.

“These families have to make the risky decisions of how much of the family budget to spend on insurance plans, often to the detriment of their own and their children’s health,” he explained. “If you believe the old adage about ‘an ounce of prevention,’ then the money we spend on preserving the health of our children will more than pay for itself in benefits of increased productivity and health care savings in the 1-2 decades later when they reach adulthood. It is time for us as a nation to come up with a more comprehensive baseline coverage for all pediatric patients and take away any barriers for families to access basic health care for children.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Peripheral manifestations contribute significantly to disease activity in adults with spondyloarthritis (SpA), point toward a generally worse prognosis, and play a big role in defining the phenotypic clustering of the heterogenous disease, according to findings from what researchers called the first prospective study “to comprehensively describe the prevalence, clinical patterns, and prognostic implications of peripheral manifestations across the entire SpA spectrum.”

The stratification of patients in the study based on the presence of peripheral manifestations (arthritis, enthesitis, and/or dactylitis) led to the identification of an endotype with unfavorable outcomes, which not only has prognostic value but supports the need for an endotype-based treatment approach rather than one centered on C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

The findings “advocate strongly for the presence of a distinct SpA endotype, based on potentially different immunopathological mechanisms and characterized by high disease activity at initial presentation with lack of substantial improvement upon follow-up,” first author Ann-Sophie De Craemer, MD, of Ghent, Belgium, and colleagues wrote.

Because the diagnostic and prognostic value of peripheral manifestations has not been well studied in SpA in general and in newly diagnosed patients in particular, Dr. De Craemer and associates decided to analyze their impact in 367 patients in the Be-Giant (BelGian Inflammatory Arthritis and spoNdylitis cohorT) cohort, a multicenter, prospective, observational cohort of newly diagnosed patients with SpA in Belgium. The study was published in Rheumatology.

The study population included 257 (70%) patients with axial-predominant SpA (axSpA) as classified by Assessment of Spondyloarthritis International Society criteria and 110 (30%) with peripheral-predominant SpA (pSpA) as defined by ASAS criteria. A total of 52 patients with axSpA had peripheral manifestations at baseline. The mean age of the patients was 34 years, and 52% were male.

The 162 patients with peripheral manifestations included 143 with arthritis, 52 with enthesitis, and 55 with dactylitis.

Two patient clusters emerge from data

In a cluster analysis that used baseline clinical features, the researchers divided the patients into cluster A (of which 242 of 248 were patients with axSpA) and cluster B (of which 104 of 119 were patients with pSpA). Most of the patients with peripheral manifestations were in cluster B (117 of 162 [72%]), compared with cluster A (45 of 162 [28%]).

A longitudinal analysis included 195 patients who completed a minimum 2-year follow-up. The longitudinal analysis identified high- and low-disease activity trajectories in each cluster.

In axSpA-predominant cluster A, patients with “high” trajectory had high disease activity levels at baseline (mean ASDAS-CRP, 3.2) that remained relatively stable, while those in the low-trajectory group (62%) had less disease activity at baseline (mean ASDAS-CRP, 2.0), which then further declined during follow-up.

Patients in the high trajectory in cluster A were more often affected by peripheral manifestations, “which remained a significant predictor in multivariate analysis,” with an odds ratio of 2.4, the researchers noted. In addition, patients with peripheral manifestations were significantly more likely to have persistent high disease activity despite starting biologics earlier than patients without peripheral manifestations (hazard ratio, 2.1).

Patients in pSpA-predominant cluster B showed differences that were similar to those seen in cluster A in terms of high– and low–disease activity trajectories (mean ASDAS-CRP of 3.6 and 2.8, respectively), but among these patients, a high level of disease activity was significantly associated with elevated CRP, rather than with peripheral disease, the researchers said.

The study findings were limited by several factors, including the exclusion of patients who did not complete the follow-up, which reduced the sample size for longitudinal analysis. However, the results were strengthened by the inclusion of patients from the full SpA spectrum, a geographically spread-out patient population, and a study design that mirrored clinical practice, the researchers noted.

The Be-Giant cohort was supported by an unrestricted grant from AbbVie. Several authors reported financial relationships with AbbVie and other pharmaceutical companies.

Peripheral manifestations contribute significantly to disease activity in adults with spondyloarthritis (SpA), point toward a generally worse prognosis, and play a big role in defining the phenotypic clustering of the heterogenous disease, according to findings from what researchers called the first prospective study “to comprehensively describe the prevalence, clinical patterns, and prognostic implications of peripheral manifestations across the entire SpA spectrum.”

The stratification of patients in the study based on the presence of peripheral manifestations (arthritis, enthesitis, and/or dactylitis) led to the identification of an endotype with unfavorable outcomes, which not only has prognostic value but supports the need for an endotype-based treatment approach rather than one centered on C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

The findings “advocate strongly for the presence of a distinct SpA endotype, based on potentially different immunopathological mechanisms and characterized by high disease activity at initial presentation with lack of substantial improvement upon follow-up,” first author Ann-Sophie De Craemer, MD, of Ghent, Belgium, and colleagues wrote.

Because the diagnostic and prognostic value of peripheral manifestations has not been well studied in SpA in general and in newly diagnosed patients in particular, Dr. De Craemer and associates decided to analyze their impact in 367 patients in the Be-Giant (BelGian Inflammatory Arthritis and spoNdylitis cohorT) cohort, a multicenter, prospective, observational cohort of newly diagnosed patients with SpA in Belgium. The study was published in Rheumatology.

The study population included 257 (70%) patients with axial-predominant SpA (axSpA) as classified by Assessment of Spondyloarthritis International Society criteria and 110 (30%) with peripheral-predominant SpA (pSpA) as defined by ASAS criteria. A total of 52 patients with axSpA had peripheral manifestations at baseline. The mean age of the patients was 34 years, and 52% were male.

The 162 patients with peripheral manifestations included 143 with arthritis, 52 with enthesitis, and 55 with dactylitis.

Two patient clusters emerge from data

In a cluster analysis that used baseline clinical features, the researchers divided the patients into cluster A (of which 242 of 248 were patients with axSpA) and cluster B (of which 104 of 119 were patients with pSpA). Most of the patients with peripheral manifestations were in cluster B (117 of 162 [72%]), compared with cluster A (45 of 162 [28%]).

A longitudinal analysis included 195 patients who completed a minimum 2-year follow-up. The longitudinal analysis identified high- and low-disease activity trajectories in each cluster.

In axSpA-predominant cluster A, patients with “high” trajectory had high disease activity levels at baseline (mean ASDAS-CRP, 3.2) that remained relatively stable, while those in the low-trajectory group (62%) had less disease activity at baseline (mean ASDAS-CRP, 2.0), which then further declined during follow-up.

Patients in the high trajectory in cluster A were more often affected by peripheral manifestations, “which remained a significant predictor in multivariate analysis,” with an odds ratio of 2.4, the researchers noted. In addition, patients with peripheral manifestations were significantly more likely to have persistent high disease activity despite starting biologics earlier than patients without peripheral manifestations (hazard ratio, 2.1).

Patients in pSpA-predominant cluster B showed differences that were similar to those seen in cluster A in terms of high– and low–disease activity trajectories (mean ASDAS-CRP of 3.6 and 2.8, respectively), but among these patients, a high level of disease activity was significantly associated with elevated CRP, rather than with peripheral disease, the researchers said.

The study findings were limited by several factors, including the exclusion of patients who did not complete the follow-up, which reduced the sample size for longitudinal analysis. However, the results were strengthened by the inclusion of patients from the full SpA spectrum, a geographically spread-out patient population, and a study design that mirrored clinical practice, the researchers noted.

The Be-Giant cohort was supported by an unrestricted grant from AbbVie. Several authors reported financial relationships with AbbVie and other pharmaceutical companies.

Peripheral manifestations contribute significantly to disease activity in adults with spondyloarthritis (SpA), point toward a generally worse prognosis, and play a big role in defining the phenotypic clustering of the heterogenous disease, according to findings from what researchers called the first prospective study “to comprehensively describe the prevalence, clinical patterns, and prognostic implications of peripheral manifestations across the entire SpA spectrum.”

The stratification of patients in the study based on the presence of peripheral manifestations (arthritis, enthesitis, and/or dactylitis) led to the identification of an endotype with unfavorable outcomes, which not only has prognostic value but supports the need for an endotype-based treatment approach rather than one centered on C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

The findings “advocate strongly for the presence of a distinct SpA endotype, based on potentially different immunopathological mechanisms and characterized by high disease activity at initial presentation with lack of substantial improvement upon follow-up,” first author Ann-Sophie De Craemer, MD, of Ghent, Belgium, and colleagues wrote.

Because the diagnostic and prognostic value of peripheral manifestations has not been well studied in SpA in general and in newly diagnosed patients in particular, Dr. De Craemer and associates decided to analyze their impact in 367 patients in the Be-Giant (BelGian Inflammatory Arthritis and spoNdylitis cohorT) cohort, a multicenter, prospective, observational cohort of newly diagnosed patients with SpA in Belgium. The study was published in Rheumatology.

The study population included 257 (70%) patients with axial-predominant SpA (axSpA) as classified by Assessment of Spondyloarthritis International Society criteria and 110 (30%) with peripheral-predominant SpA (pSpA) as defined by ASAS criteria. A total of 52 patients with axSpA had peripheral manifestations at baseline. The mean age of the patients was 34 years, and 52% were male.

The 162 patients with peripheral manifestations included 143 with arthritis, 52 with enthesitis, and 55 with dactylitis.

Two patient clusters emerge from data

In a cluster analysis that used baseline clinical features, the researchers divided the patients into cluster A (of which 242 of 248 were patients with axSpA) and cluster B (of which 104 of 119 were patients with pSpA). Most of the patients with peripheral manifestations were in cluster B (117 of 162 [72%]), compared with cluster A (45 of 162 [28%]).

A longitudinal analysis included 195 patients who completed a minimum 2-year follow-up. The longitudinal analysis identified high- and low-disease activity trajectories in each cluster.

In axSpA-predominant cluster A, patients with “high” trajectory had high disease activity levels at baseline (mean ASDAS-CRP, 3.2) that remained relatively stable, while those in the low-trajectory group (62%) had less disease activity at baseline (mean ASDAS-CRP, 2.0), which then further declined during follow-up.

Patients in the high trajectory in cluster A were more often affected by peripheral manifestations, “which remained a significant predictor in multivariate analysis,” with an odds ratio of 2.4, the researchers noted. In addition, patients with peripheral manifestations were significantly more likely to have persistent high disease activity despite starting biologics earlier than patients without peripheral manifestations (hazard ratio, 2.1).

Patients in pSpA-predominant cluster B showed differences that were similar to those seen in cluster A in terms of high– and low–disease activity trajectories (mean ASDAS-CRP of 3.6 and 2.8, respectively), but among these patients, a high level of disease activity was significantly associated with elevated CRP, rather than with peripheral disease, the researchers said.

The study findings were limited by several factors, including the exclusion of patients who did not complete the follow-up, which reduced the sample size for longitudinal analysis. However, the results were strengthened by the inclusion of patients from the full SpA spectrum, a geographically spread-out patient population, and a study design that mirrored clinical practice, the researchers noted.

The Be-Giant cohort was supported by an unrestricted grant from AbbVie. Several authors reported financial relationships with AbbVie and other pharmaceutical companies.

Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.

Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.

Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.

The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.

Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.

The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).

When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.

These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.

In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.

The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.

The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.

The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.

“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
 

Findings support value of vaccination for children with asthma

“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.

“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.

Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.

“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.

“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.

Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.

The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.

Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.

Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.

Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.

The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.

Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.

The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).

When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.

These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.

In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.

The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.

The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.

The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.

“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
 

Findings support value of vaccination for children with asthma

“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.

“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.

Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.

“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.

“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.

Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.

The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.

Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.

Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.

Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.

The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.

Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.

The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).

When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.

These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.

In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.

The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.

The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.

The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.

“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
 

Findings support value of vaccination for children with asthma

“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.

“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.

Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.

“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.

“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.

Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.

The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.

Both sickle cell trait and sickle cell disease were significantly associated with an increased risk of stillbirth, based on data from more than 50,000 women.

Pregnant women with sickle cell disease (SCD) are at increased risk of complications, including stillbirth, but many women with the disease in the United States lack access to specialty care, Silvia P. Canelón, PhD, of the University of Pennsylvania, Philadelphia, and colleagues wrote. Sickle cell trait (SCT), defined as one abnormal allele of the hemoglobin gene, is not considered a disease state because many carriers are asymptomatic, and therefore even less likely to be assessed for potential complications. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia. This condition can lead to severe medical complications for sickle cell carriers, including fetal loss, splenic infarction, exercise-related sudden death, and others,” they noted.

In a study published in JAMA Network Open, the researchers reviewed data from 63,334 deliveries in 50,560 women between Jan. 1, 2010, and Aug. 15, 2017, at four quaternary academic medical centers in Pennsylvania. Of these, 1,904 had SCT but not SCD, and 164 had SCD. The mean age of the women was 29.5 years, and approximately 56% were single at the time of delivery. A majority (87%) of the study population was Rhesus-factor positive, 47.0% were Black or African American, 33.7% were White, and 45.2% had ABO blood type O.

Risk factors for stillbirth used in the analysis included SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (to represent parity), history of cesarean delivery, multiple gestation, age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Overall, the prevalence of stillbirth in women with SCT was 1.1%, compared with 0.8% in the general study population, and was significantly associated with increased risk of stillbirth after controlling for multiple risk factors. The adjusted odds ratio was 8.94 for stillbirth risk in women with SCT, compared with women without SCT (P = .045), although the risk was greater among women with SCD, compared with those without SCD (aOR, 26.40).

“In addition, the stratified analysis found Black or African American patients with SCD to be at higher risk of stillbirth, compared with Black or African American patients without SCD (aOR, 3.59),” but no significant association was noted between stillbirth and SCT, the researchers wrote. Stillbirth rates were 1.1% in Black or African American women overall, 2.7% in those with SCD, and 1.0% in those with SCT. Overall, multiple gestation was associated with an increased risk of stillbirth (aOR, 4.68), while a history of cesarean delivery and being married at the time of delivery were associated with decreased risk (aOR, 0.44 and 0.72, respectively).

The lack of association between stillbirth and SCT in Black or African American patients supports some previous research, but contradicts other studies, the researchers wrote. “Ultimately, it may be impossible to disentangle the risks due to the disease and those due to disparities associated with the disease that have resulted from longstanding inequity and stigma,” they said. The findings also suggest that biological mechanisms of SCT may contribute to severe clinical complications, and therefore “invite a more critical examination of the assumption that SCT is not a disease state.”

The study findings were limited by several factors including the lack of assessment of SCT independent of other comorbidities, such as hypertension, preeclampsia, diabetes, and obesity, and by the use of billing codes that could misclassify patients, the researchers noted.

However, the results support some findings from previous studies of the potential health complications for pregnant SCT patients. The large study population highlights the need to identify women’s SCT status during obstetric care, and to provide both pregnancy guidance for SCT patients and systemic support of comprehensive care for SCD and SCT patients, they concluded.

Disparities may drive stillbirth in sickle cell trait women

“There is a paucity of research evaluating sickle cell trait and the risk of adverse pregnancy outcomes such as stillbirth,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Prior studies evaluating the risk of stillbirth have yielded mixed results, and an increased risk of stillbirth in women with sickle cell trait has not been established. This study is unique in that it attempts to address how racial inequities and health disparities may contribute to risk of stillbirth in women with sickle cell trait.”

Although the study findings suggest an increased risk of stillbirth in women with sickle cell trait, an analysis stratified for Black or African American patients showed no association, Dr. Krishna said. “The prevalence of stillbirth was noted to be 1% among Black or African American patients with sickle cell trait compared to the prevalence of stillbirth of 1.1% among Black or African American women with no sickle cell trait or disease. Although, sickle cell trait or sickle cell disease can be found in any racial or ethnic group, it disproportionately affects Black or African Americans, with a sickle cell trait carrier rate of approximately 1 in 10. The mixed findings in this study amongst racial/ethnic groups further suggest that there is more research needed before an association between stillbirth and sickle cell trait can be supported.”

As for clinical implications, “it is well established that for women with sickle cell trait there is an increased risk of urinary tract infections in pregnancy,” said Dr. Krishna. “Women with sickle cell trait should have a urine culture performed at their first prenatal visit and each trimester. At this time, studies evaluating risk of stillbirth in women with sickle cell trait have yielded conflicting results, and current consensus is that women with sickle cell trait are not at increased risk. In comparison, women with sickle cell disease are at increased risk for stillbirth and adverse pregnancy outcomes. Women with sickle cell disease should be followed closely during pregnancy and fetal surveillance implemented at 32 weeks, if not sooner, to reduce risk of stillbirth.

“Prior studies evaluating risk of stillbirth in women with sickle cell trait consist of retrospective cohorts with small study populations,” Dr. Krishna added. Notably, the current study was limited by the inability to adjust for comorbidities including diabetes, hypertension, and obesity, that are not only associated with an increased risk for stillbirth, but also disproportionately common among Black women.

“More studies are needed evaluating the relationship between these comorbidities as well as studies specifically evaluating how race affects care and pregnancy outcomes,” Dr. Krisha emphasized.

The study was funded by the University of Pennsylvania department of biostatistics, epidemiology, and informatics. Lead author Dr. Canelón disclosed grants from the Centers for Disease Control and Prevention, Clinical and Translational Science Awards, and grants from the National Institutes of Health outside the submitted work. Dr. Krishna had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

Both sickle cell trait and sickle cell disease were significantly associated with an increased risk of stillbirth, based on data from more than 50,000 women.

Pregnant women with sickle cell disease (SCD) are at increased risk of complications, including stillbirth, but many women with the disease in the United States lack access to specialty care, Silvia P. Canelón, PhD, of the University of Pennsylvania, Philadelphia, and colleagues wrote. Sickle cell trait (SCT), defined as one abnormal allele of the hemoglobin gene, is not considered a disease state because many carriers are asymptomatic, and therefore even less likely to be assessed for potential complications. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia. This condition can lead to severe medical complications for sickle cell carriers, including fetal loss, splenic infarction, exercise-related sudden death, and others,” they noted.

In a study published in JAMA Network Open, the researchers reviewed data from 63,334 deliveries in 50,560 women between Jan. 1, 2010, and Aug. 15, 2017, at four quaternary academic medical centers in Pennsylvania. Of these, 1,904 had SCT but not SCD, and 164 had SCD. The mean age of the women was 29.5 years, and approximately 56% were single at the time of delivery. A majority (87%) of the study population was Rhesus-factor positive, 47.0% were Black or African American, 33.7% were White, and 45.2% had ABO blood type O.

Risk factors for stillbirth used in the analysis included SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (to represent parity), history of cesarean delivery, multiple gestation, age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Overall, the prevalence of stillbirth in women with SCT was 1.1%, compared with 0.8% in the general study population, and was significantly associated with increased risk of stillbirth after controlling for multiple risk factors. The adjusted odds ratio was 8.94 for stillbirth risk in women with SCT, compared with women without SCT (P = .045), although the risk was greater among women with SCD, compared with those without SCD (aOR, 26.40).

“In addition, the stratified analysis found Black or African American patients with SCD to be at higher risk of stillbirth, compared with Black or African American patients without SCD (aOR, 3.59),” but no significant association was noted between stillbirth and SCT, the researchers wrote. Stillbirth rates were 1.1% in Black or African American women overall, 2.7% in those with SCD, and 1.0% in those with SCT. Overall, multiple gestation was associated with an increased risk of stillbirth (aOR, 4.68), while a history of cesarean delivery and being married at the time of delivery were associated with decreased risk (aOR, 0.44 and 0.72, respectively).

The lack of association between stillbirth and SCT in Black or African American patients supports some previous research, but contradicts other studies, the researchers wrote. “Ultimately, it may be impossible to disentangle the risks due to the disease and those due to disparities associated with the disease that have resulted from longstanding inequity and stigma,” they said. The findings also suggest that biological mechanisms of SCT may contribute to severe clinical complications, and therefore “invite a more critical examination of the assumption that SCT is not a disease state.”

The study findings were limited by several factors including the lack of assessment of SCT independent of other comorbidities, such as hypertension, preeclampsia, diabetes, and obesity, and by the use of billing codes that could misclassify patients, the researchers noted.

However, the results support some findings from previous studies of the potential health complications for pregnant SCT patients. The large study population highlights the need to identify women’s SCT status during obstetric care, and to provide both pregnancy guidance for SCT patients and systemic support of comprehensive care for SCD and SCT patients, they concluded.

Disparities may drive stillbirth in sickle cell trait women

“There is a paucity of research evaluating sickle cell trait and the risk of adverse pregnancy outcomes such as stillbirth,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Prior studies evaluating the risk of stillbirth have yielded mixed results, and an increased risk of stillbirth in women with sickle cell trait has not been established. This study is unique in that it attempts to address how racial inequities and health disparities may contribute to risk of stillbirth in women with sickle cell trait.”

Although the study findings suggest an increased risk of stillbirth in women with sickle cell trait, an analysis stratified for Black or African American patients showed no association, Dr. Krishna said. “The prevalence of stillbirth was noted to be 1% among Black or African American patients with sickle cell trait compared to the prevalence of stillbirth of 1.1% among Black or African American women with no sickle cell trait or disease. Although, sickle cell trait or sickle cell disease can be found in any racial or ethnic group, it disproportionately affects Black or African Americans, with a sickle cell trait carrier rate of approximately 1 in 10. The mixed findings in this study amongst racial/ethnic groups further suggest that there is more research needed before an association between stillbirth and sickle cell trait can be supported.”

As for clinical implications, “it is well established that for women with sickle cell trait there is an increased risk of urinary tract infections in pregnancy,” said Dr. Krishna. “Women with sickle cell trait should have a urine culture performed at their first prenatal visit and each trimester. At this time, studies evaluating risk of stillbirth in women with sickle cell trait have yielded conflicting results, and current consensus is that women with sickle cell trait are not at increased risk. In comparison, women with sickle cell disease are at increased risk for stillbirth and adverse pregnancy outcomes. Women with sickle cell disease should be followed closely during pregnancy and fetal surveillance implemented at 32 weeks, if not sooner, to reduce risk of stillbirth.

“Prior studies evaluating risk of stillbirth in women with sickle cell trait consist of retrospective cohorts with small study populations,” Dr. Krishna added. Notably, the current study was limited by the inability to adjust for comorbidities including diabetes, hypertension, and obesity, that are not only associated with an increased risk for stillbirth, but also disproportionately common among Black women.

“More studies are needed evaluating the relationship between these comorbidities as well as studies specifically evaluating how race affects care and pregnancy outcomes,” Dr. Krisha emphasized.

The study was funded by the University of Pennsylvania department of biostatistics, epidemiology, and informatics. Lead author Dr. Canelón disclosed grants from the Centers for Disease Control and Prevention, Clinical and Translational Science Awards, and grants from the National Institutes of Health outside the submitted work. Dr. Krishna had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

Both sickle cell trait and sickle cell disease were significantly associated with an increased risk of stillbirth, based on data from more than 50,000 women.

Pregnant women with sickle cell disease (SCD) are at increased risk of complications, including stillbirth, but many women with the disease in the United States lack access to specialty care, Silvia P. Canelón, PhD, of the University of Pennsylvania, Philadelphia, and colleagues wrote. Sickle cell trait (SCT), defined as one abnormal allele of the hemoglobin gene, is not considered a disease state because many carriers are asymptomatic, and therefore even less likely to be assessed for potential complications. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia. This condition can lead to severe medical complications for sickle cell carriers, including fetal loss, splenic infarction, exercise-related sudden death, and others,” they noted.

In a study published in JAMA Network Open, the researchers reviewed data from 63,334 deliveries in 50,560 women between Jan. 1, 2010, and Aug. 15, 2017, at four quaternary academic medical centers in Pennsylvania. Of these, 1,904 had SCT but not SCD, and 164 had SCD. The mean age of the women was 29.5 years, and approximately 56% were single at the time of delivery. A majority (87%) of the study population was Rhesus-factor positive, 47.0% were Black or African American, 33.7% were White, and 45.2% had ABO blood type O.

Risk factors for stillbirth used in the analysis included SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (to represent parity), history of cesarean delivery, multiple gestation, age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Overall, the prevalence of stillbirth in women with SCT was 1.1%, compared with 0.8% in the general study population, and was significantly associated with increased risk of stillbirth after controlling for multiple risk factors. The adjusted odds ratio was 8.94 for stillbirth risk in women with SCT, compared with women without SCT (P = .045), although the risk was greater among women with SCD, compared with those without SCD (aOR, 26.40).

“In addition, the stratified analysis found Black or African American patients with SCD to be at higher risk of stillbirth, compared with Black or African American patients without SCD (aOR, 3.59),” but no significant association was noted between stillbirth and SCT, the researchers wrote. Stillbirth rates were 1.1% in Black or African American women overall, 2.7% in those with SCD, and 1.0% in those with SCT. Overall, multiple gestation was associated with an increased risk of stillbirth (aOR, 4.68), while a history of cesarean delivery and being married at the time of delivery were associated with decreased risk (aOR, 0.44 and 0.72, respectively).

The lack of association between stillbirth and SCT in Black or African American patients supports some previous research, but contradicts other studies, the researchers wrote. “Ultimately, it may be impossible to disentangle the risks due to the disease and those due to disparities associated with the disease that have resulted from longstanding inequity and stigma,” they said. The findings also suggest that biological mechanisms of SCT may contribute to severe clinical complications, and therefore “invite a more critical examination of the assumption that SCT is not a disease state.”

The study findings were limited by several factors including the lack of assessment of SCT independent of other comorbidities, such as hypertension, preeclampsia, diabetes, and obesity, and by the use of billing codes that could misclassify patients, the researchers noted.

However, the results support some findings from previous studies of the potential health complications for pregnant SCT patients. The large study population highlights the need to identify women’s SCT status during obstetric care, and to provide both pregnancy guidance for SCT patients and systemic support of comprehensive care for SCD and SCT patients, they concluded.

Disparities may drive stillbirth in sickle cell trait women

“There is a paucity of research evaluating sickle cell trait and the risk of adverse pregnancy outcomes such as stillbirth,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Prior studies evaluating the risk of stillbirth have yielded mixed results, and an increased risk of stillbirth in women with sickle cell trait has not been established. This study is unique in that it attempts to address how racial inequities and health disparities may contribute to risk of stillbirth in women with sickle cell trait.”

Although the study findings suggest an increased risk of stillbirth in women with sickle cell trait, an analysis stratified for Black or African American patients showed no association, Dr. Krishna said. “The prevalence of stillbirth was noted to be 1% among Black or African American patients with sickle cell trait compared to the prevalence of stillbirth of 1.1% among Black or African American women with no sickle cell trait or disease. Although, sickle cell trait or sickle cell disease can be found in any racial or ethnic group, it disproportionately affects Black or African Americans, with a sickle cell trait carrier rate of approximately 1 in 10. The mixed findings in this study amongst racial/ethnic groups further suggest that there is more research needed before an association between stillbirth and sickle cell trait can be supported.”

As for clinical implications, “it is well established that for women with sickle cell trait there is an increased risk of urinary tract infections in pregnancy,” said Dr. Krishna. “Women with sickle cell trait should have a urine culture performed at their first prenatal visit and each trimester. At this time, studies evaluating risk of stillbirth in women with sickle cell trait have yielded conflicting results, and current consensus is that women with sickle cell trait are not at increased risk. In comparison, women with sickle cell disease are at increased risk for stillbirth and adverse pregnancy outcomes. Women with sickle cell disease should be followed closely during pregnancy and fetal surveillance implemented at 32 weeks, if not sooner, to reduce risk of stillbirth.

“Prior studies evaluating risk of stillbirth in women with sickle cell trait consist of retrospective cohorts with small study populations,” Dr. Krishna added. Notably, the current study was limited by the inability to adjust for comorbidities including diabetes, hypertension, and obesity, that are not only associated with an increased risk for stillbirth, but also disproportionately common among Black women.

“More studies are needed evaluating the relationship between these comorbidities as well as studies specifically evaluating how race affects care and pregnancy outcomes,” Dr. Krisha emphasized.

The study was funded by the University of Pennsylvania department of biostatistics, epidemiology, and informatics. Lead author Dr. Canelón disclosed grants from the Centers for Disease Control and Prevention, Clinical and Translational Science Awards, and grants from the National Institutes of Health outside the submitted work. Dr. Krishna had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

The Odoribacter splanchnicus strain of human donor-derived bacteria correlated with clinical response to ulcerative colitis in study in which mouse models were colonized with patient-derived strains.

Although some recent trials have shown the effectiveness of fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC), the current process is limited by the used of crude donor fecal material, which increases the risk of infection and decreases potential effectiveness, Svetlana Lima, MD, of Weill Cornell Medicine, New York, and colleagues wrote.

“Rational selection and production of specific microbial strains or communities could improve efficacy, minimize the risk of adverse reactions as well as increase the acceptance of microbiome-based therapies,” the researchers wrote.

In a study published in Gastroenterology, the researchers used metagenomic analysis and IgA sequencing (for sorting and sequencing IgA-coated microbiota) to identify a core of transferable and IgA-coated microbiota. They conducted metagenomic sequencing on 60 stool samples, including 20 recipient-participants with active UC who were treated with FMT, and another 20 FMT recipients with data from 4 weeks after FMT from a previously reported trial.

The core transferable microbiota (CTM) included 22 species of bacteria at 4 weeks after FMT. To determine a relationship between CTM and clinical response to FMT, the researchers defined clinical response as a decrease in Mayo score of 3 or greater with a rectal bleeding score of 1 or less by 4 weeks after FMT; 35% of study participants met this endpoint.* A total of 20 species were unique to the responders. “Of the donor-derived genera, only the relative abundance of Odoribacter at [week 4] post FMT and its increase post FMT was found to significantly correlate with decrease in Mayo score,” the researchers noted.

The researchers then colonized germ-free or genetically engineered mice with patient-derived bacterial strains.

O. splanchnicus also increased induction of interleukin-10, and increased the production of short-chain fatty acids. Taken together, these factors allowed for O. splanchnicus to limit colitis in the mice.

The study findings represent the first strain-level analysis of FMT in UC participants, and define a transferable microbiota associated with clinical response that could serve as a prognostic biomarker, the researchers noted in their discussion section. Although analysis revealed 12 donor-derived bacterial species that predicted clinical response, further IgA analysis identified O. splanchnicus as “the only microbe within the responders core that correlates with clinical response and highlights the potential impact of this taxa seen in independent cohorts, as well as mouse models of colitis and colorectal cancer,” the researchers emphasized.

The study findings were limited by the small sample size and the lack of prospective data. However, “collectively, this work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O. splanchnicus as a key component, which mechanistically promotes protection through both cellular and metabolic function,” the researchers said. “These mechanistic features will help enable desperately needed strategies to enhance therapeutic efficacy of microbial therapy for UC.”
 

Study strains improve effectiveness

“There is an accumulating body of evidence that suggests that gut dysbiosis, or the imbalance between good and bad microbes, plays an important role in the pathogenesis and progression of ulcerative colitis,” Jeffrey Berinstein, MD, of the University of Michigan, Ann Arbor, said in an interview. “It is for this reason that therapeutic manipulation of gut microbiota with fecal microbiota transplant is being explored as a potential treatment option for UC. FMT has demonstrated promise for ulcerative colitis, however little is known about the specific microbiota strains contributing to this observed improvement. In this study, the authors aimed to better understand the mechanisms and the specific strains in FMT contributing to this observed improvement, which is an important step toward improving efficacy and minimizing the risk of adverse events related to FMT in the future.”

Dr. Berinstein was surprised that O. splanchnicus was the only microbe identified that correlated with clinical response. “Previous studies have suggested that microbial diversity is a key factor in successful response to FMT,” he noted. “FMT remains an important potential nonpharmacologic treatment strategy for ulcerative colitis, however more research is needed to understand the mechanism and to develop safer and more efficacious methods for delivering FMT.” Specifically, prospective studies are needed to explore the efficacy and safety of FMT enriched in strains of O. splanchnicus to confirm the current study findings.

The current study is important at this time because, although microbial transferability has emerged as a potential to treat IBD, “the mechanistic understanding of microbial transferability and engraftment has been lacking,” Atsushi Sakuraba, MD, PhD of the University of Chicago, said in an interview. “I was surprised that the effectiveness of FMT in UC could be narrowed down to O. splanchnicus.” The current take-home message for clinicians is that, although FMT currently uses crude donor fecal material, it may soon use more selected microbial strains. However, “whether transfer of O. splanchnicus alone or enriched fecal material provide improved efficacy and safety need to be analyzed,” he added.

The study was supported by Boehringer Ingelheim, the National Institutes of Health, the Kenneth Rainin Foundation, and the Charina Foundation. One coauthor disclosed grant support from Boehringer Ingelheim for this study, and several coauthors are employees of Boehringer Ingelheim. Neither Dr. Berinstein nor Dr. Sakuraba had no financial conflicts to disclose.

This article was updated Dec. 1, 2021.

*Correction, 4/11/22: An earlier version of this article misstated the definition of clinical response.

The Odoribacter splanchnicus strain of human donor-derived bacteria correlated with clinical response to ulcerative colitis in study in which mouse models were colonized with patient-derived strains.

Although some recent trials have shown the effectiveness of fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC), the current process is limited by the used of crude donor fecal material, which increases the risk of infection and decreases potential effectiveness, Svetlana Lima, MD, of Weill Cornell Medicine, New York, and colleagues wrote.

“Rational selection and production of specific microbial strains or communities could improve efficacy, minimize the risk of adverse reactions as well as increase the acceptance of microbiome-based therapies,” the researchers wrote.

In a study published in Gastroenterology, the researchers used metagenomic analysis and IgA sequencing (for sorting and sequencing IgA-coated microbiota) to identify a core of transferable and IgA-coated microbiota. They conducted metagenomic sequencing on 60 stool samples, including 20 recipient-participants with active UC who were treated with FMT, and another 20 FMT recipients with data from 4 weeks after FMT from a previously reported trial.

The core transferable microbiota (CTM) included 22 species of bacteria at 4 weeks after FMT. To determine a relationship between CTM and clinical response to FMT, the researchers defined clinical response as a decrease in Mayo score of 3 or greater with a rectal bleeding score of 1 or less by 4 weeks after FMT; 35% of study participants met this endpoint.* A total of 20 species were unique to the responders. “Of the donor-derived genera, only the relative abundance of Odoribacter at [week 4] post FMT and its increase post FMT was found to significantly correlate with decrease in Mayo score,” the researchers noted.

The researchers then colonized germ-free or genetically engineered mice with patient-derived bacterial strains.

O. splanchnicus also increased induction of interleukin-10, and increased the production of short-chain fatty acids. Taken together, these factors allowed for O. splanchnicus to limit colitis in the mice.

The study findings represent the first strain-level analysis of FMT in UC participants, and define a transferable microbiota associated with clinical response that could serve as a prognostic biomarker, the researchers noted in their discussion section. Although analysis revealed 12 donor-derived bacterial species that predicted clinical response, further IgA analysis identified O. splanchnicus as “the only microbe within the responders core that correlates with clinical response and highlights the potential impact of this taxa seen in independent cohorts, as well as mouse models of colitis and colorectal cancer,” the researchers emphasized.

The study findings were limited by the small sample size and the lack of prospective data. However, “collectively, this work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O. splanchnicus as a key component, which mechanistically promotes protection through both cellular and metabolic function,” the researchers said. “These mechanistic features will help enable desperately needed strategies to enhance therapeutic efficacy of microbial therapy for UC.”
 

Study strains improve effectiveness

“There is an accumulating body of evidence that suggests that gut dysbiosis, or the imbalance between good and bad microbes, plays an important role in the pathogenesis and progression of ulcerative colitis,” Jeffrey Berinstein, MD, of the University of Michigan, Ann Arbor, said in an interview. “It is for this reason that therapeutic manipulation of gut microbiota with fecal microbiota transplant is being explored as a potential treatment option for UC. FMT has demonstrated promise for ulcerative colitis, however little is known about the specific microbiota strains contributing to this observed improvement. In this study, the authors aimed to better understand the mechanisms and the specific strains in FMT contributing to this observed improvement, which is an important step toward improving efficacy and minimizing the risk of adverse events related to FMT in the future.”

Dr. Berinstein was surprised that O. splanchnicus was the only microbe identified that correlated with clinical response. “Previous studies have suggested that microbial diversity is a key factor in successful response to FMT,” he noted. “FMT remains an important potential nonpharmacologic treatment strategy for ulcerative colitis, however more research is needed to understand the mechanism and to develop safer and more efficacious methods for delivering FMT.” Specifically, prospective studies are needed to explore the efficacy and safety of FMT enriched in strains of O. splanchnicus to confirm the current study findings.

The current study is important at this time because, although microbial transferability has emerged as a potential to treat IBD, “the mechanistic understanding of microbial transferability and engraftment has been lacking,” Atsushi Sakuraba, MD, PhD of the University of Chicago, said in an interview. “I was surprised that the effectiveness of FMT in UC could be narrowed down to O. splanchnicus.” The current take-home message for clinicians is that, although FMT currently uses crude donor fecal material, it may soon use more selected microbial strains. However, “whether transfer of O. splanchnicus alone or enriched fecal material provide improved efficacy and safety need to be analyzed,” he added.

The study was supported by Boehringer Ingelheim, the National Institutes of Health, the Kenneth Rainin Foundation, and the Charina Foundation. One coauthor disclosed grant support from Boehringer Ingelheim for this study, and several coauthors are employees of Boehringer Ingelheim. Neither Dr. Berinstein nor Dr. Sakuraba had no financial conflicts to disclose.

This article was updated Dec. 1, 2021.

*Correction, 4/11/22: An earlier version of this article misstated the definition of clinical response.

The Odoribacter splanchnicus strain of human donor-derived bacteria correlated with clinical response to ulcerative colitis in study in which mouse models were colonized with patient-derived strains.

Although some recent trials have shown the effectiveness of fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC), the current process is limited by the used of crude donor fecal material, which increases the risk of infection and decreases potential effectiveness, Svetlana Lima, MD, of Weill Cornell Medicine, New York, and colleagues wrote.

“Rational selection and production of specific microbial strains or communities could improve efficacy, minimize the risk of adverse reactions as well as increase the acceptance of microbiome-based therapies,” the researchers wrote.

In a study published in Gastroenterology, the researchers used metagenomic analysis and IgA sequencing (for sorting and sequencing IgA-coated microbiota) to identify a core of transferable and IgA-coated microbiota. They conducted metagenomic sequencing on 60 stool samples, including 20 recipient-participants with active UC who were treated with FMT, and another 20 FMT recipients with data from 4 weeks after FMT from a previously reported trial.

The core transferable microbiota (CTM) included 22 species of bacteria at 4 weeks after FMT. To determine a relationship between CTM and clinical response to FMT, the researchers defined clinical response as a decrease in Mayo score of 3 or greater with a rectal bleeding score of 1 or less by 4 weeks after FMT; 35% of study participants met this endpoint.* A total of 20 species were unique to the responders. “Of the donor-derived genera, only the relative abundance of Odoribacter at [week 4] post FMT and its increase post FMT was found to significantly correlate with decrease in Mayo score,” the researchers noted.

The researchers then colonized germ-free or genetically engineered mice with patient-derived bacterial strains.

O. splanchnicus also increased induction of interleukin-10, and increased the production of short-chain fatty acids. Taken together, these factors allowed for O. splanchnicus to limit colitis in the mice.

The study findings represent the first strain-level analysis of FMT in UC participants, and define a transferable microbiota associated with clinical response that could serve as a prognostic biomarker, the researchers noted in their discussion section. Although analysis revealed 12 donor-derived bacterial species that predicted clinical response, further IgA analysis identified O. splanchnicus as “the only microbe within the responders core that correlates with clinical response and highlights the potential impact of this taxa seen in independent cohorts, as well as mouse models of colitis and colorectal cancer,” the researchers emphasized.

The study findings were limited by the small sample size and the lack of prospective data. However, “collectively, this work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O. splanchnicus as a key component, which mechanistically promotes protection through both cellular and metabolic function,” the researchers said. “These mechanistic features will help enable desperately needed strategies to enhance therapeutic efficacy of microbial therapy for UC.”
 

Study strains improve effectiveness

“There is an accumulating body of evidence that suggests that gut dysbiosis, or the imbalance between good and bad microbes, plays an important role in the pathogenesis and progression of ulcerative colitis,” Jeffrey Berinstein, MD, of the University of Michigan, Ann Arbor, said in an interview. “It is for this reason that therapeutic manipulation of gut microbiota with fecal microbiota transplant is being explored as a potential treatment option for UC. FMT has demonstrated promise for ulcerative colitis, however little is known about the specific microbiota strains contributing to this observed improvement. In this study, the authors aimed to better understand the mechanisms and the specific strains in FMT contributing to this observed improvement, which is an important step toward improving efficacy and minimizing the risk of adverse events related to FMT in the future.”

Dr. Berinstein was surprised that O. splanchnicus was the only microbe identified that correlated with clinical response. “Previous studies have suggested that microbial diversity is a key factor in successful response to FMT,” he noted. “FMT remains an important potential nonpharmacologic treatment strategy for ulcerative colitis, however more research is needed to understand the mechanism and to develop safer and more efficacious methods for delivering FMT.” Specifically, prospective studies are needed to explore the efficacy and safety of FMT enriched in strains of O. splanchnicus to confirm the current study findings.

The current study is important at this time because, although microbial transferability has emerged as a potential to treat IBD, “the mechanistic understanding of microbial transferability and engraftment has been lacking,” Atsushi Sakuraba, MD, PhD of the University of Chicago, said in an interview. “I was surprised that the effectiveness of FMT in UC could be narrowed down to O. splanchnicus.” The current take-home message for clinicians is that, although FMT currently uses crude donor fecal material, it may soon use more selected microbial strains. However, “whether transfer of O. splanchnicus alone or enriched fecal material provide improved efficacy and safety need to be analyzed,” he added.

The study was supported by Boehringer Ingelheim, the National Institutes of Health, the Kenneth Rainin Foundation, and the Charina Foundation. One coauthor disclosed grant support from Boehringer Ingelheim for this study, and several coauthors are employees of Boehringer Ingelheim. Neither Dr. Berinstein nor Dr. Sakuraba had no financial conflicts to disclose.

This article was updated Dec. 1, 2021.

*Correction, 4/11/22: An earlier version of this article misstated the definition of clinical response.

Higher poverty concentration at the county level significantly increased the risk of firearm-related deaths in children and youth aged 5-24 years in the United States, based on a review of approximately 67,000 fatalities.

Firearms are the second-leading cause of death in children and young adults in the United States, according to data from the Centers for Disease Control and Prevention, wrote Jefferson T. Barrett, MD, of The Children’s Hospital at Montefiore, New York, and colleagues. County-level poverty has been associated with increased injury mortality in children, but the association between county-level poverty and firearm-related mortality in particular has not been well studied.

In a cross-sectional study published in JAMA Pediatrics, 67,905 firearm-related deaths in children and youth aged 5-24 years that occurred between Jan. 1, 2007, and Dec. 31, 2016 were analyzed. The deaths included 42,512 homicides (62.6%), 23,034 suicides (33.9%), and 1,627 unintentional deaths (2.4%).

County poverty data were acquired from the U.S. Census Bureau. County-level poverty was divided into five categories based on percentage of the population living below the federal poverty level: 0%-4.9%, 5%-9.9%, 10%-14.9%, 15%-19.9%, and 20% or more.

Overall, 88.6% of the total deaths were in males. Notably, 44.8% of total firearm-related deaths and 63.9% of homicides occurred in non-Hispanic Blacks, who make up only 14% of the youth population in the United States, the researchers wrote.

The total number of firearm-related deaths was 248 in the lowest quintile of poverty concentration, followed by 6,841, 18,551, 27,305, and 14,960 in the remaining quintiles.

In a multivariate regression model that included demographics, urban versus rural, and statewide firearm prevalence, youth in counties with the highest quintile of poverty concentration had an increased rate of total firearm-related deaths (adjusted incidence rate ratio, 2.29), as well as increased rates of homicides, suicides, and unintentional deaths (aIRR, 3.55, 1.45, and 9.32, respectively), compared with those living in the lowest quintile of poverty concentration. Individuals in the highest poverty quintile accounted for 22.0% of total firearm-related deaths, 25.5% of homicides, 15.3% of suicides, and 25.1% of unintentional deaths.

The researchers also calculated the population-attributable fraction (PAF) and years of potential life lost. “The PAF represents the proportion of deaths associated with a particular exposure, which was concentrated county poverty in this study,” they explained. The PAF for all firearm-related deaths was 0.51, PAFs for homicides, suicides, and unintentional deaths were 0.66, 0.30, and 0.86, respectively. The PAF calculation translated to 34,292 firearm-related deaths that may not have occurred if youth in all counties had the same risk as those in counties with the lowest poverty concentration.

“Over the 10-year study period, we observed 3,833,105 years of potential life lost in youth aged 5-24 years from firearm-related deaths,” the researchers wrote.

The study findings were limited by several factors including the potential bias of a cross-section design, and inability to account for all the ways that county-level poverty might increase the risk of firearm-related death in children and teens, the researchers noted. Other potential limitations include possible misclassification of death, lack of data on individual family incomes, shifts in counties in the poverty categories over time, and the use of statewide, rather than countywide, estimates of firearm ownership.

However, the results are consistent with those of previous studies, and add that “mortality rates were consistent even after controlling for demographic variables, county urbanicity, and statewide firearm prevalence,” the researchers concluded.
 

Address structural racism to reduce disparities

“Firearm-related homicides among youth aged 5-24 years are among the causes of death with the greatest disparities,” based on CDC fatal injury reports, wrote Alice M. Ellyson, PhD, Frederick P. Rivara, MD, and Ali Rowhani-Rahbar, MD, all of the University of Washington, Seattle, in an accompanying editorial.

The current study builds on previous research, including studies showing an association between income inequality and firearm-related homicide, they said. More research is needed to determine how to intervene in the pathways between poverty and firearm-related death. For example, if access to high-quality health care is a factor, programs to increase access to health insurance, such as the Affordable Care Act and Children’s Health Insurance Program, or to increase access to high-quality trauma care may help reduce firearm-related death in youth.

“The study of where, how, and why racism operates as a factor in both poverty and firearm-related death must continue, especially considering the disparities consistently documented in Alaska Native or American Indian, Black, and Hispanic communities,” the editorialists wrote.

“Key potential mechanisms for reducing the consequences of poverty for firearm-related death are often denied to racial and ethnic minority groups through a variety of structures, policies, and systems in health care, employment, housing, transportation, and education,” they emphasized, and the impact of racism, not only on the pathways to poverty, but also on mediators between poverty and firearm-related death, must be explored.

Findings spotlight need to for poverty programs

The study was an interesting look at the specific relationship between poverty and firearm-related deaths in people aged younger than 25 years in the United States, Tim Joos, MD, of Seattle said in an interview.

“Although America is not a poor country, the combination of poverty within America and its unique gun culture seems to prove deadly for its youth,” Dr. Joos said. “The strongest relationship is between firearm-related homicide and poverty, but unintentional firearm deaths and poverty also are clearly linked, whereas the link between firearm-related suicide and poverty appears to be present, but small.”.

In the current study, “the authors note that firearm deaths are the second-leading cause of death among all people ages 15-24 years,” said Dr. Joos. “Many of us have followed children from infancy just to have them meet this untimely end as adolescents, wishing we had a vaccine or other remedy in our toolbelt for this particular scourge.

“As our country currently debates the size of the social safety net, this study is one of many that suggests government programs aimed at poverty alleviation would substantially contribute to the health of American youth,” Dr. Joos added.

The study received no outside funding. Lead author Dr. Barrett had no financial conflicts to disclose. Dr. Ellyson disclosed funds from the CDC, the state of Washington, and the Grandmothers Against Gun Violence Foundation for research outside the submitted work. Dr. Rivara disclosed funds from the National Institutes of Health, the State of Washington, and the National Collaborative on Gun Violence Research for research outside the submitted work. Dr. Rowhani-Rahbar disclosed funds from the CDC, National Institutes of Health, National Collaborative on Gun Violence Research, Fund for a Safer Future, and state of Washington for research outside the submitted work. Dr. Joos had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.

Higher poverty concentration at the county level significantly increased the risk of firearm-related deaths in children and youth aged 5-24 years in the United States, based on a review of approximately 67,000 fatalities.

Firearms are the second-leading cause of death in children and young adults in the United States, according to data from the Centers for Disease Control and Prevention, wrote Jefferson T. Barrett, MD, of The Children’s Hospital at Montefiore, New York, and colleagues. County-level poverty has been associated with increased injury mortality in children, but the association between county-level poverty and firearm-related mortality in particular has not been well studied.

In a cross-sectional study published in JAMA Pediatrics, 67,905 firearm-related deaths in children and youth aged 5-24 years that occurred between Jan. 1, 2007, and Dec. 31, 2016 were analyzed. The deaths included 42,512 homicides (62.6%), 23,034 suicides (33.9%), and 1,627 unintentional deaths (2.4%).

County poverty data were acquired from the U.S. Census Bureau. County-level poverty was divided into five categories based on percentage of the population living below the federal poverty level: 0%-4.9%, 5%-9.9%, 10%-14.9%, 15%-19.9%, and 20% or more.

Overall, 88.6% of the total deaths were in males. Notably, 44.8% of total firearm-related deaths and 63.9% of homicides occurred in non-Hispanic Blacks, who make up only 14% of the youth population in the United States, the researchers wrote.

The total number of firearm-related deaths was 248 in the lowest quintile of poverty concentration, followed by 6,841, 18,551, 27,305, and 14,960 in the remaining quintiles.

In a multivariate regression model that included demographics, urban versus rural, and statewide firearm prevalence, youth in counties with the highest quintile of poverty concentration had an increased rate of total firearm-related deaths (adjusted incidence rate ratio, 2.29), as well as increased rates of homicides, suicides, and unintentional deaths (aIRR, 3.55, 1.45, and 9.32, respectively), compared with those living in the lowest quintile of poverty concentration. Individuals in the highest poverty quintile accounted for 22.0% of total firearm-related deaths, 25.5% of homicides, 15.3% of suicides, and 25.1% of unintentional deaths.

The researchers also calculated the population-attributable fraction (PAF) and years of potential life lost. “The PAF represents the proportion of deaths associated with a particular exposure, which was concentrated county poverty in this study,” they explained. The PAF for all firearm-related deaths was 0.51, PAFs for homicides, suicides, and unintentional deaths were 0.66, 0.30, and 0.86, respectively. The PAF calculation translated to 34,292 firearm-related deaths that may not have occurred if youth in all counties had the same risk as those in counties with the lowest poverty concentration.

“Over the 10-year study period, we observed 3,833,105 years of potential life lost in youth aged 5-24 years from firearm-related deaths,” the researchers wrote.

The study findings were limited by several factors including the potential bias of a cross-section design, and inability to account for all the ways that county-level poverty might increase the risk of firearm-related death in children and teens, the researchers noted. Other potential limitations include possible misclassification of death, lack of data on individual family incomes, shifts in counties in the poverty categories over time, and the use of statewide, rather than countywide, estimates of firearm ownership.

However, the results are consistent with those of previous studies, and add that “mortality rates were consistent even after controlling for demographic variables, county urbanicity, and statewide firearm prevalence,” the researchers concluded.
 

Address structural racism to reduce disparities

“Firearm-related homicides among youth aged 5-24 years are among the causes of death with the greatest disparities,” based on CDC fatal injury reports, wrote Alice M. Ellyson, PhD, Frederick P. Rivara, MD, and Ali Rowhani-Rahbar, MD, all of the University of Washington, Seattle, in an accompanying editorial.

The current study builds on previous research, including studies showing an association between income inequality and firearm-related homicide, they said. More research is needed to determine how to intervene in the pathways between poverty and firearm-related death. For example, if access to high-quality health care is a factor, programs to increase access to health insurance, such as the Affordable Care Act and Children’s Health Insurance Program, or to increase access to high-quality trauma care may help reduce firearm-related death in youth.

“The study of where, how, and why racism operates as a factor in both poverty and firearm-related death must continue, especially considering the disparities consistently documented in Alaska Native or American Indian, Black, and Hispanic communities,” the editorialists wrote.

“Key potential mechanisms for reducing the consequences of poverty for firearm-related death are often denied to racial and ethnic minority groups through a variety of structures, policies, and systems in health care, employment, housing, transportation, and education,” they emphasized, and the impact of racism, not only on the pathways to poverty, but also on mediators between poverty and firearm-related death, must be explored.

Findings spotlight need to for poverty programs

The study was an interesting look at the specific relationship between poverty and firearm-related deaths in people aged younger than 25 years in the United States, Tim Joos, MD, of Seattle said in an interview.

“Although America is not a poor country, the combination of poverty within America and its unique gun culture seems to prove deadly for its youth,” Dr. Joos said. “The strongest relationship is between firearm-related homicide and poverty, but unintentional firearm deaths and poverty also are clearly linked, whereas the link between firearm-related suicide and poverty appears to be present, but small.”.

In the current study, “the authors note that firearm deaths are the second-leading cause of death among all people ages 15-24 years,” said Dr. Joos. “Many of us have followed children from infancy just to have them meet this untimely end as adolescents, wishing we had a vaccine or other remedy in our toolbelt for this particular scourge.

“As our country currently debates the size of the social safety net, this study is one of many that suggests government programs aimed at poverty alleviation would substantially contribute to the health of American youth,” Dr. Joos added.

The study received no outside funding. Lead author Dr. Barrett had no financial conflicts to disclose. Dr. Ellyson disclosed funds from the CDC, the state of Washington, and the Grandmothers Against Gun Violence Foundation for research outside the submitted work. Dr. Rivara disclosed funds from the National Institutes of Health, the State of Washington, and the National Collaborative on Gun Violence Research for research outside the submitted work. Dr. Rowhani-Rahbar disclosed funds from the CDC, National Institutes of Health, National Collaborative on Gun Violence Research, Fund for a Safer Future, and state of Washington for research outside the submitted work. Dr. Joos had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.

Higher poverty concentration at the county level significantly increased the risk of firearm-related deaths in children and youth aged 5-24 years in the United States, based on a review of approximately 67,000 fatalities.

Firearms are the second-leading cause of death in children and young adults in the United States, according to data from the Centers for Disease Control and Prevention, wrote Jefferson T. Barrett, MD, of The Children’s Hospital at Montefiore, New York, and colleagues. County-level poverty has been associated with increased injury mortality in children, but the association between county-level poverty and firearm-related mortality in particular has not been well studied.

In a cross-sectional study published in JAMA Pediatrics, 67,905 firearm-related deaths in children and youth aged 5-24 years that occurred between Jan. 1, 2007, and Dec. 31, 2016 were analyzed. The deaths included 42,512 homicides (62.6%), 23,034 suicides (33.9%), and 1,627 unintentional deaths (2.4%).

County poverty data were acquired from the U.S. Census Bureau. County-level poverty was divided into five categories based on percentage of the population living below the federal poverty level: 0%-4.9%, 5%-9.9%, 10%-14.9%, 15%-19.9%, and 20% or more.

Overall, 88.6% of the total deaths were in males. Notably, 44.8% of total firearm-related deaths and 63.9% of homicides occurred in non-Hispanic Blacks, who make up only 14% of the youth population in the United States, the researchers wrote.

The total number of firearm-related deaths was 248 in the lowest quintile of poverty concentration, followed by 6,841, 18,551, 27,305, and 14,960 in the remaining quintiles.

In a multivariate regression model that included demographics, urban versus rural, and statewide firearm prevalence, youth in counties with the highest quintile of poverty concentration had an increased rate of total firearm-related deaths (adjusted incidence rate ratio, 2.29), as well as increased rates of homicides, suicides, and unintentional deaths (aIRR, 3.55, 1.45, and 9.32, respectively), compared with those living in the lowest quintile of poverty concentration. Individuals in the highest poverty quintile accounted for 22.0% of total firearm-related deaths, 25.5% of homicides, 15.3% of suicides, and 25.1% of unintentional deaths.

The researchers also calculated the population-attributable fraction (PAF) and years of potential life lost. “The PAF represents the proportion of deaths associated with a particular exposure, which was concentrated county poverty in this study,” they explained. The PAF for all firearm-related deaths was 0.51, PAFs for homicides, suicides, and unintentional deaths were 0.66, 0.30, and 0.86, respectively. The PAF calculation translated to 34,292 firearm-related deaths that may not have occurred if youth in all counties had the same risk as those in counties with the lowest poverty concentration.

“Over the 10-year study period, we observed 3,833,105 years of potential life lost in youth aged 5-24 years from firearm-related deaths,” the researchers wrote.

The study findings were limited by several factors including the potential bias of a cross-section design, and inability to account for all the ways that county-level poverty might increase the risk of firearm-related death in children and teens, the researchers noted. Other potential limitations include possible misclassification of death, lack of data on individual family incomes, shifts in counties in the poverty categories over time, and the use of statewide, rather than countywide, estimates of firearm ownership.

However, the results are consistent with those of previous studies, and add that “mortality rates were consistent even after controlling for demographic variables, county urbanicity, and statewide firearm prevalence,” the researchers concluded.
 

Address structural racism to reduce disparities

“Firearm-related homicides among youth aged 5-24 years are among the causes of death with the greatest disparities,” based on CDC fatal injury reports, wrote Alice M. Ellyson, PhD, Frederick P. Rivara, MD, and Ali Rowhani-Rahbar, MD, all of the University of Washington, Seattle, in an accompanying editorial.

The current study builds on previous research, including studies showing an association between income inequality and firearm-related homicide, they said. More research is needed to determine how to intervene in the pathways between poverty and firearm-related death. For example, if access to high-quality health care is a factor, programs to increase access to health insurance, such as the Affordable Care Act and Children’s Health Insurance Program, or to increase access to high-quality trauma care may help reduce firearm-related death in youth.

“The study of where, how, and why racism operates as a factor in both poverty and firearm-related death must continue, especially considering the disparities consistently documented in Alaska Native or American Indian, Black, and Hispanic communities,” the editorialists wrote.

“Key potential mechanisms for reducing the consequences of poverty for firearm-related death are often denied to racial and ethnic minority groups through a variety of structures, policies, and systems in health care, employment, housing, transportation, and education,” they emphasized, and the impact of racism, not only on the pathways to poverty, but also on mediators between poverty and firearm-related death, must be explored.

Findings spotlight need to for poverty programs

The study was an interesting look at the specific relationship between poverty and firearm-related deaths in people aged younger than 25 years in the United States, Tim Joos, MD, of Seattle said in an interview.

“Although America is not a poor country, the combination of poverty within America and its unique gun culture seems to prove deadly for its youth,” Dr. Joos said. “The strongest relationship is between firearm-related homicide and poverty, but unintentional firearm deaths and poverty also are clearly linked, whereas the link between firearm-related suicide and poverty appears to be present, but small.”.

In the current study, “the authors note that firearm deaths are the second-leading cause of death among all people ages 15-24 years,” said Dr. Joos. “Many of us have followed children from infancy just to have them meet this untimely end as adolescents, wishing we had a vaccine or other remedy in our toolbelt for this particular scourge.

“As our country currently debates the size of the social safety net, this study is one of many that suggests government programs aimed at poverty alleviation would substantially contribute to the health of American youth,” Dr. Joos added.

The study received no outside funding. Lead author Dr. Barrett had no financial conflicts to disclose. Dr. Ellyson disclosed funds from the CDC, the state of Washington, and the Grandmothers Against Gun Violence Foundation for research outside the submitted work. Dr. Rivara disclosed funds from the National Institutes of Health, the State of Washington, and the National Collaborative on Gun Violence Research for research outside the submitted work. Dr. Rowhani-Rahbar disclosed funds from the CDC, National Institutes of Health, National Collaborative on Gun Violence Research, Fund for a Safer Future, and state of Washington for research outside the submitted work. Dr. Joos had no financial conflicts to disclose, but serves on the editorial advisory board of Pediatric News.