Heidi Splete

Long-term data showed negligible differences in mortality among hypertensive adults treated with thiazide-type diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors in a review of nearly 33,000 individuals published in JAMA Network Open.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was designed to compare initial antihypertensive treatments with a calcium channel blocker (CCB; amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or an alpha-blocker (doxazosin), and a thiazide-type diuretic (chlorthalidone).

The composite primary outcome was fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), but long-term data were lacking, wrote Jose-Miguel Yamal, PhD, of University of Texas Health Science Center at Houston, and colleagues. A previous study with 8-13 years of follow-up showed no significant differences in mortality between the treatment groups, the researchers noted.

In the current study, a prespecified secondary analysis of ALLHAT, the researchers added 11 more years of data for a total of 19-24 years of follow-up after randomization.

In the original ALLHAT, 32,804 adults aged 55 years and older with a diagnosis of hypertension and at least one additional coronary heart disease risk factor were followed for 4-8 years for all-cause mortality. A subgroup of 22,754 were followed for fatal or nonfatal cardiovascular disease (CVD) for a mean of 13.7 years, with a maximum of 23.9 years.

The study occurred from Feb. 23, 1994, to Dec. 31, 2017. The participants were randomized to receive a thiazide-type diuretic (15,002 patients), a CCB (8,898 patients), or an ACE inhibitor (8,904 patients).

The primary outcome was CVD mortality; secondary outcomes included all-cause mortality, combined fatal and nonfatal CVD (CVD morbidity), and both morbidity and mortality for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

At 23 years, CVD mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively. The adjusted hazard ratios were 0.97 for CCB vs. diuretics and 1.06 for ACE inhibitors vs. diuretics.

Although the risk of stroke mortality and of combined fatal and nonfatal hospitalized stroke was higher in the ACE inhibitor group compared with the diuretic group (adjusted hazard ratios 1.19 and 1.11, respectively), this increase was no longer significant after adjustment for multiple comparisons. “In contrast to the in-trial and 8-year to 13-year analyses, we now observed that the lisinopril group had an increased risk of kidney disease mortality that emerged after approximately 13 years after randomization, but this effect was attenuated after adjustment for baseline variables,” the researchers wrote in their discussion.

The findings were limited by several factors including the potential effect of unblinding if participants stopped the randomized drug, and by the lack of morbidity and mortality data on Canadian participants, Veterans Affairs participants, and those with no Medicare number, the researchers noted. Other limitations included the lack of data on posttrial medication use, blood pressure, and laboratory findings, they said.

However, the results over the follow-up period of up to 23 years supported those of the larger ALLHAT study, with similar outcomes among the drugs, and with 11 years of passive follow-up, “the results for lisinopril vs. chlorthalidone for stroke and stroke mortality are almost the same,” they concluded.
 

Findings support current practice, but new drug data are needed

The current study was important to determine whether there was a significant difference in long-term morbidity and mortality between patients treated with thiazide diuretics, calcium channel blockers and ACE inhibitors, Noel Deep, MD, said in an interview.

“Previously reported data had indicated no significant differences between patients randomized to one of these three classes of antihypertensive medications during the trial period or at 8-13 years post trial,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep is chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

“This study reinforces the previously noted benefits of the three classes of antihypertensive medications, as well as the higher rates of cardiovascular disease and stroke in the ACE inhibitor arm,” he said.

In clinical practice, the results suggest that thiazide diuretics should be considered first-line agents for management of hypertension based on their noninferiority compared with ACE inhibitors and CCBs, and lower risk of stroke compared with ACE inhibitors, Dr. Deep said in an interview. “All three classes of antihypertensive medications are equally efficacious in blood pressure control and preventing all-cause mortality,” he said.

More research is needed in the wake of the introduction of other classes of antihypertensives since the original ALLHAT trial, Dr. Deep said. “It would be beneficial to assess the relative benefit/risks of those medications compared to the thiazide diuretics, and I would also look at studies comparing beta blockers to the thiazide diuretics,” he said. The question remains as to whether outcomes were affected by patients’ use of other classes of antihypertensives after the trial period, he said.

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the editorial advisory board of Internal Medicine News.

Long-term data showed negligible differences in mortality among hypertensive adults treated with thiazide-type diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors in a review of nearly 33,000 individuals published in JAMA Network Open.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was designed to compare initial antihypertensive treatments with a calcium channel blocker (CCB; amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or an alpha-blocker (doxazosin), and a thiazide-type diuretic (chlorthalidone).

The composite primary outcome was fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), but long-term data were lacking, wrote Jose-Miguel Yamal, PhD, of University of Texas Health Science Center at Houston, and colleagues. A previous study with 8-13 years of follow-up showed no significant differences in mortality between the treatment groups, the researchers noted.

In the current study, a prespecified secondary analysis of ALLHAT, the researchers added 11 more years of data for a total of 19-24 years of follow-up after randomization.

In the original ALLHAT, 32,804 adults aged 55 years and older with a diagnosis of hypertension and at least one additional coronary heart disease risk factor were followed for 4-8 years for all-cause mortality. A subgroup of 22,754 were followed for fatal or nonfatal cardiovascular disease (CVD) for a mean of 13.7 years, with a maximum of 23.9 years.

The study occurred from Feb. 23, 1994, to Dec. 31, 2017. The participants were randomized to receive a thiazide-type diuretic (15,002 patients), a CCB (8,898 patients), or an ACE inhibitor (8,904 patients).

The primary outcome was CVD mortality; secondary outcomes included all-cause mortality, combined fatal and nonfatal CVD (CVD morbidity), and both morbidity and mortality for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

At 23 years, CVD mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively. The adjusted hazard ratios were 0.97 for CCB vs. diuretics and 1.06 for ACE inhibitors vs. diuretics.

Although the risk of stroke mortality and of combined fatal and nonfatal hospitalized stroke was higher in the ACE inhibitor group compared with the diuretic group (adjusted hazard ratios 1.19 and 1.11, respectively), this increase was no longer significant after adjustment for multiple comparisons. “In contrast to the in-trial and 8-year to 13-year analyses, we now observed that the lisinopril group had an increased risk of kidney disease mortality that emerged after approximately 13 years after randomization, but this effect was attenuated after adjustment for baseline variables,” the researchers wrote in their discussion.

The findings were limited by several factors including the potential effect of unblinding if participants stopped the randomized drug, and by the lack of morbidity and mortality data on Canadian participants, Veterans Affairs participants, and those with no Medicare number, the researchers noted. Other limitations included the lack of data on posttrial medication use, blood pressure, and laboratory findings, they said.

However, the results over the follow-up period of up to 23 years supported those of the larger ALLHAT study, with similar outcomes among the drugs, and with 11 years of passive follow-up, “the results for lisinopril vs. chlorthalidone for stroke and stroke mortality are almost the same,” they concluded.
 

Findings support current practice, but new drug data are needed

The current study was important to determine whether there was a significant difference in long-term morbidity and mortality between patients treated with thiazide diuretics, calcium channel blockers and ACE inhibitors, Noel Deep, MD, said in an interview.

“Previously reported data had indicated no significant differences between patients randomized to one of these three classes of antihypertensive medications during the trial period or at 8-13 years post trial,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep is chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

“This study reinforces the previously noted benefits of the three classes of antihypertensive medications, as well as the higher rates of cardiovascular disease and stroke in the ACE inhibitor arm,” he said.

In clinical practice, the results suggest that thiazide diuretics should be considered first-line agents for management of hypertension based on their noninferiority compared with ACE inhibitors and CCBs, and lower risk of stroke compared with ACE inhibitors, Dr. Deep said in an interview. “All three classes of antihypertensive medications are equally efficacious in blood pressure control and preventing all-cause mortality,” he said.

More research is needed in the wake of the introduction of other classes of antihypertensives since the original ALLHAT trial, Dr. Deep said. “It would be beneficial to assess the relative benefit/risks of those medications compared to the thiazide diuretics, and I would also look at studies comparing beta blockers to the thiazide diuretics,” he said. The question remains as to whether outcomes were affected by patients’ use of other classes of antihypertensives after the trial period, he said.

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the editorial advisory board of Internal Medicine News.

Long-term data showed negligible differences in mortality among hypertensive adults treated with thiazide-type diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors in a review of nearly 33,000 individuals published in JAMA Network Open.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was designed to compare initial antihypertensive treatments with a calcium channel blocker (CCB; amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or an alpha-blocker (doxazosin), and a thiazide-type diuretic (chlorthalidone).

The composite primary outcome was fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), but long-term data were lacking, wrote Jose-Miguel Yamal, PhD, of University of Texas Health Science Center at Houston, and colleagues. A previous study with 8-13 years of follow-up showed no significant differences in mortality between the treatment groups, the researchers noted.

In the current study, a prespecified secondary analysis of ALLHAT, the researchers added 11 more years of data for a total of 19-24 years of follow-up after randomization.

In the original ALLHAT, 32,804 adults aged 55 years and older with a diagnosis of hypertension and at least one additional coronary heart disease risk factor were followed for 4-8 years for all-cause mortality. A subgroup of 22,754 were followed for fatal or nonfatal cardiovascular disease (CVD) for a mean of 13.7 years, with a maximum of 23.9 years.

The study occurred from Feb. 23, 1994, to Dec. 31, 2017. The participants were randomized to receive a thiazide-type diuretic (15,002 patients), a CCB (8,898 patients), or an ACE inhibitor (8,904 patients).

The primary outcome was CVD mortality; secondary outcomes included all-cause mortality, combined fatal and nonfatal CVD (CVD morbidity), and both morbidity and mortality for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

At 23 years, CVD mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively. The adjusted hazard ratios were 0.97 for CCB vs. diuretics and 1.06 for ACE inhibitors vs. diuretics.

Although the risk of stroke mortality and of combined fatal and nonfatal hospitalized stroke was higher in the ACE inhibitor group compared with the diuretic group (adjusted hazard ratios 1.19 and 1.11, respectively), this increase was no longer significant after adjustment for multiple comparisons. “In contrast to the in-trial and 8-year to 13-year analyses, we now observed that the lisinopril group had an increased risk of kidney disease mortality that emerged after approximately 13 years after randomization, but this effect was attenuated after adjustment for baseline variables,” the researchers wrote in their discussion.

The findings were limited by several factors including the potential effect of unblinding if participants stopped the randomized drug, and by the lack of morbidity and mortality data on Canadian participants, Veterans Affairs participants, and those with no Medicare number, the researchers noted. Other limitations included the lack of data on posttrial medication use, blood pressure, and laboratory findings, they said.

However, the results over the follow-up period of up to 23 years supported those of the larger ALLHAT study, with similar outcomes among the drugs, and with 11 years of passive follow-up, “the results for lisinopril vs. chlorthalidone for stroke and stroke mortality are almost the same,” they concluded.
 

Findings support current practice, but new drug data are needed

The current study was important to determine whether there was a significant difference in long-term morbidity and mortality between patients treated with thiazide diuretics, calcium channel blockers and ACE inhibitors, Noel Deep, MD, said in an interview.

“Previously reported data had indicated no significant differences between patients randomized to one of these three classes of antihypertensive medications during the trial period or at 8-13 years post trial,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep is chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

“This study reinforces the previously noted benefits of the three classes of antihypertensive medications, as well as the higher rates of cardiovascular disease and stroke in the ACE inhibitor arm,” he said.

In clinical practice, the results suggest that thiazide diuretics should be considered first-line agents for management of hypertension based on their noninferiority compared with ACE inhibitors and CCBs, and lower risk of stroke compared with ACE inhibitors, Dr. Deep said in an interview. “All three classes of antihypertensive medications are equally efficacious in blood pressure control and preventing all-cause mortality,” he said.

More research is needed in the wake of the introduction of other classes of antihypertensives since the original ALLHAT trial, Dr. Deep said. “It would be beneficial to assess the relative benefit/risks of those medications compared to the thiazide diuretics, and I would also look at studies comparing beta blockers to the thiazide diuretics,” he said. The question remains as to whether outcomes were affected by patients’ use of other classes of antihypertensives after the trial period, he said.

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the editorial advisory board of Internal Medicine News.

Follicular occlusion, mast cell disease, and eczema were common presentations among patients with hypermobile Ehlers-Danlos syndrome (hEDS), in a study of nearly 500 individuals.

The genetic cause of hEDS, a common inherited connective tissue disorder, remains unknown, wrote Alan Snyder, MD, of the department of dermatology and dermatologic surgery at Medical University of South Carolina, Charleston, and colleagues.

Previous research suggests that changes in dermal mechanics predispose these patients to a range of skin conditions including mast cell activation disorder (MCAD) spectrum and chronic spontaneous urticaria, abnormal scars or wound healing, piezogenic papules, dyshidrosis, skin laxity or softness, easy bruising, local anesthesia resistance, keratosis pilaris, striae, and hidradenitis suppurativa, the researchers wrote.

However, data on these and other dermatologic manifestations of hEDS are limited, they said.

The diagnosis of hEDS will continue to be made more frequently and carefully, as the condition becomes more recognized and understood in the medical community, especially with anticipated capabilities of genetic testing, Dr. Snyder said in an interview.

“Being able to be aware of disease-specific comorbidities, such as those discovered in this study, allows providers to better stratify phenotypes and improve patient disease co-management,” he said.

In the study, published in the Journal of the American Academy of Dermatology, the researchers reviewed data on 1,364 patients with ICD-10 or ICD-9 codes for hEDS or EDS unspecified who were seen at a single institution between June 2005 and May 2022. Most of the patients were White (95.4%) and female (86.7%); the average age was 29.2 years.

Of the 1,364 patients included in the chart review, 497 (36.4%) had documented skin manifestations. Of these, 118 (24.2%) had disorders of follicular occlusion (12 had hidradenitis suppurativa, 32 had folliculitis, and 74 had acne); 112 (23%) had eczema or atopic dermatitis, 98 (19.7%) had mast cell disorder, 32 (6.4%) had psoriasis, and 32 (6.4%) had wound healing issues (16 had hypertrophic keloids/scarring, 5 had abscesses, 3 had abnormal bruising, and 8 had other would healing issues).

The study also included results of a multiple-choice patient survey from 1,354 individuals. In the survey, approximately two-thirds of patients reported abnormal scarring, abnormal wound healing, and cutaneous laxity (61.7%, 69.0%, and 71.0%, respectively).

The findings were limited by several factors including the retrospective study design, lack of testing to confirm hEDS diagnosis, and the potential interdisciplinary selection bias for diagnoses, the authors noted.

However, the results support previous studies showing increased rates of occlusive conditions in hEDS and higher rates of acne, folliculitis, and psoriasis, and highlight the need for clinician education to manage patients and promote better outcomes, the researchers concluded.

Data Enhance Clinical Awareness

“Given the increasingly understood relation between TH2-directed and mast-cell mediated diseases and hEDS, it was not necessarily a surprise to find the increased prevalence of atopy and mast cell disease, but rather an interesting confirmation, within the limitations that exist with retrospective chart review,” Dr. Snyder told this news organization. “While it may make some intuitive sense that certain cohorts with higher risk of HS may have a higher risk of acne, this had not been reported in the literature to date,” he noted. “Given the high levels of patient reported issues with scarring and wound healing, I was surprised that so few analogous diagnoses were physician-reported in the medical records.”

In clinical practice, “health care professionals and patients need to be aware hEDS is associated with high rates of eczematous, mast-cell mediated and follicular occlusive cutaneous disorders,” Dr. Snyder said in an interview. “There seems to be a discrepancy between patients and physician awareness of scarring or wound healing issues in this patient population,” he added.

Looking ahead, “we need to better research and characterize the various hEDS phenotypes to understand who is at highest risk for various TH2-mediated or follicular occlusive disorders,” said Dr. Snyder. “Moreover, a greater understanding is needed of the wound healing inadequacies that predispose these patients to poor outcomes during dermatologic surgery,” he said.

The study was supported by the Ehlers-Danlos Society and the Milton and Tamar Maltz Family Foundation. The researchers had no financial conflicts to disclose.

Follicular occlusion, mast cell disease, and eczema were common presentations among patients with hypermobile Ehlers-Danlos syndrome (hEDS), in a study of nearly 500 individuals.

The genetic cause of hEDS, a common inherited connective tissue disorder, remains unknown, wrote Alan Snyder, MD, of the department of dermatology and dermatologic surgery at Medical University of South Carolina, Charleston, and colleagues.

Previous research suggests that changes in dermal mechanics predispose these patients to a range of skin conditions including mast cell activation disorder (MCAD) spectrum and chronic spontaneous urticaria, abnormal scars or wound healing, piezogenic papules, dyshidrosis, skin laxity or softness, easy bruising, local anesthesia resistance, keratosis pilaris, striae, and hidradenitis suppurativa, the researchers wrote.

However, data on these and other dermatologic manifestations of hEDS are limited, they said.

The diagnosis of hEDS will continue to be made more frequently and carefully, as the condition becomes more recognized and understood in the medical community, especially with anticipated capabilities of genetic testing, Dr. Snyder said in an interview.

“Being able to be aware of disease-specific comorbidities, such as those discovered in this study, allows providers to better stratify phenotypes and improve patient disease co-management,” he said.

In the study, published in the Journal of the American Academy of Dermatology, the researchers reviewed data on 1,364 patients with ICD-10 or ICD-9 codes for hEDS or EDS unspecified who were seen at a single institution between June 2005 and May 2022. Most of the patients were White (95.4%) and female (86.7%); the average age was 29.2 years.

Of the 1,364 patients included in the chart review, 497 (36.4%) had documented skin manifestations. Of these, 118 (24.2%) had disorders of follicular occlusion (12 had hidradenitis suppurativa, 32 had folliculitis, and 74 had acne); 112 (23%) had eczema or atopic dermatitis, 98 (19.7%) had mast cell disorder, 32 (6.4%) had psoriasis, and 32 (6.4%) had wound healing issues (16 had hypertrophic keloids/scarring, 5 had abscesses, 3 had abnormal bruising, and 8 had other would healing issues).

The study also included results of a multiple-choice patient survey from 1,354 individuals. In the survey, approximately two-thirds of patients reported abnormal scarring, abnormal wound healing, and cutaneous laxity (61.7%, 69.0%, and 71.0%, respectively).

The findings were limited by several factors including the retrospective study design, lack of testing to confirm hEDS diagnosis, and the potential interdisciplinary selection bias for diagnoses, the authors noted.

However, the results support previous studies showing increased rates of occlusive conditions in hEDS and higher rates of acne, folliculitis, and psoriasis, and highlight the need for clinician education to manage patients and promote better outcomes, the researchers concluded.

Data Enhance Clinical Awareness

“Given the increasingly understood relation between TH2-directed and mast-cell mediated diseases and hEDS, it was not necessarily a surprise to find the increased prevalence of atopy and mast cell disease, but rather an interesting confirmation, within the limitations that exist with retrospective chart review,” Dr. Snyder told this news organization. “While it may make some intuitive sense that certain cohorts with higher risk of HS may have a higher risk of acne, this had not been reported in the literature to date,” he noted. “Given the high levels of patient reported issues with scarring and wound healing, I was surprised that so few analogous diagnoses were physician-reported in the medical records.”

In clinical practice, “health care professionals and patients need to be aware hEDS is associated with high rates of eczematous, mast-cell mediated and follicular occlusive cutaneous disorders,” Dr. Snyder said in an interview. “There seems to be a discrepancy between patients and physician awareness of scarring or wound healing issues in this patient population,” he added.

Looking ahead, “we need to better research and characterize the various hEDS phenotypes to understand who is at highest risk for various TH2-mediated or follicular occlusive disorders,” said Dr. Snyder. “Moreover, a greater understanding is needed of the wound healing inadequacies that predispose these patients to poor outcomes during dermatologic surgery,” he said.

The study was supported by the Ehlers-Danlos Society and the Milton and Tamar Maltz Family Foundation. The researchers had no financial conflicts to disclose.

Follicular occlusion, mast cell disease, and eczema were common presentations among patients with hypermobile Ehlers-Danlos syndrome (hEDS), in a study of nearly 500 individuals.

The genetic cause of hEDS, a common inherited connective tissue disorder, remains unknown, wrote Alan Snyder, MD, of the department of dermatology and dermatologic surgery at Medical University of South Carolina, Charleston, and colleagues.

Previous research suggests that changes in dermal mechanics predispose these patients to a range of skin conditions including mast cell activation disorder (MCAD) spectrum and chronic spontaneous urticaria, abnormal scars or wound healing, piezogenic papules, dyshidrosis, skin laxity or softness, easy bruising, local anesthesia resistance, keratosis pilaris, striae, and hidradenitis suppurativa, the researchers wrote.

However, data on these and other dermatologic manifestations of hEDS are limited, they said.

The diagnosis of hEDS will continue to be made more frequently and carefully, as the condition becomes more recognized and understood in the medical community, especially with anticipated capabilities of genetic testing, Dr. Snyder said in an interview.

“Being able to be aware of disease-specific comorbidities, such as those discovered in this study, allows providers to better stratify phenotypes and improve patient disease co-management,” he said.

In the study, published in the Journal of the American Academy of Dermatology, the researchers reviewed data on 1,364 patients with ICD-10 or ICD-9 codes for hEDS or EDS unspecified who were seen at a single institution between June 2005 and May 2022. Most of the patients were White (95.4%) and female (86.7%); the average age was 29.2 years.

Of the 1,364 patients included in the chart review, 497 (36.4%) had documented skin manifestations. Of these, 118 (24.2%) had disorders of follicular occlusion (12 had hidradenitis suppurativa, 32 had folliculitis, and 74 had acne); 112 (23%) had eczema or atopic dermatitis, 98 (19.7%) had mast cell disorder, 32 (6.4%) had psoriasis, and 32 (6.4%) had wound healing issues (16 had hypertrophic keloids/scarring, 5 had abscesses, 3 had abnormal bruising, and 8 had other would healing issues).

The study also included results of a multiple-choice patient survey from 1,354 individuals. In the survey, approximately two-thirds of patients reported abnormal scarring, abnormal wound healing, and cutaneous laxity (61.7%, 69.0%, and 71.0%, respectively).

The findings were limited by several factors including the retrospective study design, lack of testing to confirm hEDS diagnosis, and the potential interdisciplinary selection bias for diagnoses, the authors noted.

However, the results support previous studies showing increased rates of occlusive conditions in hEDS and higher rates of acne, folliculitis, and psoriasis, and highlight the need for clinician education to manage patients and promote better outcomes, the researchers concluded.

Data Enhance Clinical Awareness

“Given the increasingly understood relation between TH2-directed and mast-cell mediated diseases and hEDS, it was not necessarily a surprise to find the increased prevalence of atopy and mast cell disease, but rather an interesting confirmation, within the limitations that exist with retrospective chart review,” Dr. Snyder told this news organization. “While it may make some intuitive sense that certain cohorts with higher risk of HS may have a higher risk of acne, this had not been reported in the literature to date,” he noted. “Given the high levels of patient reported issues with scarring and wound healing, I was surprised that so few analogous diagnoses were physician-reported in the medical records.”

In clinical practice, “health care professionals and patients need to be aware hEDS is associated with high rates of eczematous, mast-cell mediated and follicular occlusive cutaneous disorders,” Dr. Snyder said in an interview. “There seems to be a discrepancy between patients and physician awareness of scarring or wound healing issues in this patient population,” he added.

Looking ahead, “we need to better research and characterize the various hEDS phenotypes to understand who is at highest risk for various TH2-mediated or follicular occlusive disorders,” said Dr. Snyder. “Moreover, a greater understanding is needed of the wound healing inadequacies that predispose these patients to poor outcomes during dermatologic surgery,” he said.

The study was supported by the Ehlers-Danlos Society and the Milton and Tamar Maltz Family Foundation. The researchers had no financial conflicts to disclose.

TOPLINE:

Salivary microbiota changes caused by cigarette smoking may affect metabolic pathways and increase disease risk.

METHODOLOGY:

The researchers analyzed health information and data on the composition of salivary microbiota from 1601 adult participants in the Cooperative Health Research in South Tyrol (CHRIS) microbiome study (CHRISMB); CHRIS is an ongoing study in Italy.

The average age of the study population was 45 years; 53% were female, and 45% were current or former smokers.

The researchers hypothesized that changes in salivary microbial composition would be associated with smoking, with more nitrate-reducing bacteria present, and that nitrate reduction pathways would be reduced in smokers.

TAKEAWAY:

The researchers identified 44 genera that differed in the salivary microbiota of current smokers and nonsmokers. In smokers, seven genera in the phylum Proteobacteria were decreased and six in the phylum Actinobacteria were increased compared with nonsmokers; these phyla contain primarily aerobic and anaerobic taxa, respectively.

Some microbiota changes were significantly associated with daily smoking intensity; genera from the classes Betaproteobacteria (Lautropia or Neisseria), Gammaproteobacteria (Cardiobacterium), and Flavobacteriia (Capnocytophaga) decreased significantly with increased grams of tobacco smoked per day, measured in 5-g increments.

Smoking was associated with changes in the salivary microbiota; the nitrate reduction pathway was significantly lower in smokers compared with nonsmokers, and these decreases were consistent with previous studies of decreased cardiovascular events in former smokers.

However, the salivary microbiota of smokers who had quit for at least 5 years resembled that of individuals who had never smoked.

IN PRACTICE:

“Decreased microbial nitrate reduction pathway abundance in smokers may provide an additional explanation for the effect of smoking on cardiovascular and periodontal diseases risk, a hypothesis which should be tested in future studies,” the researchers wrote.

SOURCE:

The lead author of the study was Giacomo Antonello, MD, of Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy. The study was published online in Scientific Reports (a Nature journal) on November 2, 2023.

LIMITATIONS:

The cross-sectional design and lack of professional assessment of tooth and gum health were limiting factors, as were potential confounding factors including medication use, diet, and alcohol intake.

DISCLOSURES:

The study was supported by the Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol and by the European Regional Development Fund. The CHRISMB microbiota data generation was funded by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

Salivary microbiota changes caused by cigarette smoking may affect metabolic pathways and increase disease risk.

METHODOLOGY:

The researchers analyzed health information and data on the composition of salivary microbiota from 1601 adult participants in the Cooperative Health Research in South Tyrol (CHRIS) microbiome study (CHRISMB); CHRIS is an ongoing study in Italy.

The average age of the study population was 45 years; 53% were female, and 45% were current or former smokers.

The researchers hypothesized that changes in salivary microbial composition would be associated with smoking, with more nitrate-reducing bacteria present, and that nitrate reduction pathways would be reduced in smokers.

TAKEAWAY:

The researchers identified 44 genera that differed in the salivary microbiota of current smokers and nonsmokers. In smokers, seven genera in the phylum Proteobacteria were decreased and six in the phylum Actinobacteria were increased compared with nonsmokers; these phyla contain primarily aerobic and anaerobic taxa, respectively.

Some microbiota changes were significantly associated with daily smoking intensity; genera from the classes Betaproteobacteria (Lautropia or Neisseria), Gammaproteobacteria (Cardiobacterium), and Flavobacteriia (Capnocytophaga) decreased significantly with increased grams of tobacco smoked per day, measured in 5-g increments.

Smoking was associated with changes in the salivary microbiota; the nitrate reduction pathway was significantly lower in smokers compared with nonsmokers, and these decreases were consistent with previous studies of decreased cardiovascular events in former smokers.

However, the salivary microbiota of smokers who had quit for at least 5 years resembled that of individuals who had never smoked.

IN PRACTICE:

“Decreased microbial nitrate reduction pathway abundance in smokers may provide an additional explanation for the effect of smoking on cardiovascular and periodontal diseases risk, a hypothesis which should be tested in future studies,” the researchers wrote.

SOURCE:

The lead author of the study was Giacomo Antonello, MD, of Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy. The study was published online in Scientific Reports (a Nature journal) on November 2, 2023.

LIMITATIONS:

The cross-sectional design and lack of professional assessment of tooth and gum health were limiting factors, as were potential confounding factors including medication use, diet, and alcohol intake.

DISCLOSURES:

The study was supported by the Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol and by the European Regional Development Fund. The CHRISMB microbiota data generation was funded by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

Salivary microbiota changes caused by cigarette smoking may affect metabolic pathways and increase disease risk.

METHODOLOGY:

The researchers analyzed health information and data on the composition of salivary microbiota from 1601 adult participants in the Cooperative Health Research in South Tyrol (CHRIS) microbiome study (CHRISMB); CHRIS is an ongoing study in Italy.

The average age of the study population was 45 years; 53% were female, and 45% were current or former smokers.

The researchers hypothesized that changes in salivary microbial composition would be associated with smoking, with more nitrate-reducing bacteria present, and that nitrate reduction pathways would be reduced in smokers.

TAKEAWAY:

The researchers identified 44 genera that differed in the salivary microbiota of current smokers and nonsmokers. In smokers, seven genera in the phylum Proteobacteria were decreased and six in the phylum Actinobacteria were increased compared with nonsmokers; these phyla contain primarily aerobic and anaerobic taxa, respectively.

Some microbiota changes were significantly associated with daily smoking intensity; genera from the classes Betaproteobacteria (Lautropia or Neisseria), Gammaproteobacteria (Cardiobacterium), and Flavobacteriia (Capnocytophaga) decreased significantly with increased grams of tobacco smoked per day, measured in 5-g increments.

Smoking was associated with changes in the salivary microbiota; the nitrate reduction pathway was significantly lower in smokers compared with nonsmokers, and these decreases were consistent with previous studies of decreased cardiovascular events in former smokers.

However, the salivary microbiota of smokers who had quit for at least 5 years resembled that of individuals who had never smoked.

IN PRACTICE:

“Decreased microbial nitrate reduction pathway abundance in smokers may provide an additional explanation for the effect of smoking on cardiovascular and periodontal diseases risk, a hypothesis which should be tested in future studies,” the researchers wrote.

SOURCE:

The lead author of the study was Giacomo Antonello, MD, of Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy. The study was published online in Scientific Reports (a Nature journal) on November 2, 2023.

LIMITATIONS:

The cross-sectional design and lack of professional assessment of tooth and gum health were limiting factors, as were potential confounding factors including medication use, diet, and alcohol intake.

DISCLOSURES:

The study was supported by the Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol and by the European Regional Development Fund. The CHRISMB microbiota data generation was funded by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

Children with asthma exposed to worsening psychosocial environmental factors during childhood were more likely to have more severe asthma symptoms than those without such exposures.

METHODOLOGY:

• The researchers reviewed data from the Longitudinal Study of Australian Children, a nationally representative cohort that also collects data on the health, psychosocial, and environmental status of parents, and used three multivariate models to assess the impact of psychosocial environmental factors on asthma symptoms at ages 1 year, 4-5 years, and 14-15 years.
• The study population included 3,917 children aged 0-15 years who were sorted into three asthma symptom trajectory groups (low/no asthma, transient high asthma, and persistent high asthma); asthma symptoms were defined as a history of chest wheezing lasting at least a week within the past 12 months.
• The researchers identified several psychosocial environmental factors as exposure variables on the basis of literature reviews; these factors were maternal depression, parents’ financial hardship, parental availability, and parental stressful life events.

TAKEAWAY:

• The mean scores of psychosocial factors for the overall study population remained stable over time, but groups of children exposed to bad trajectories of psychosocial factors were significantly more likely to have transient high and persistent high asthma symptoms.
• In the first year of life, only parents’ stressful life events were significantly associated with the persistent high asthma symptom trajectory group in an adjusted analysis.
• At age 4-5 years, maternal depression, low parental availability, and parents’ stressful life events were significantly associated with persistent high asthma; parents’ financial hardship was significantly associated with transient high asthma symptoms.
• At age 14-15 years, children exposed to “moderate and increasing” maternal depression, “moderate and declining” parents’ financial hardship, and “moderate and increasing” parents’ stressful life events were significantly associated with persistent high asthma versus no or low asthma, with relative risk ratios of 1.55, 1.40, and 1.77, respectively.

IN PRACTICE:

The study findings highlight the need for policy makers to take action to improve asthma control in children by reducing exposure to harmful psychosocial environmental factors, the researchers concluded.

SOURCE:

The lead author of the study was K.M. Shahunja, MBBS, PhD candidate at the University of Queensland, Brisbane, Australia. The study was published online in Pediatric Pulmonology.

LIMITATIONS:

The study is the first known to examine asthma symptom trajectories at different developmental stages, but participant attrition and missing values were limiting factors, as was the inability to account for all potential psychosocial environmental factors that might influence asthma symptoms in childhood.

DISCLOSURES:

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

A version of this article first appeared on Medscape.com.

TOPLINE:

Children with asthma exposed to worsening psychosocial environmental factors during childhood were more likely to have more severe asthma symptoms than those without such exposures.

METHODOLOGY:

• The researchers reviewed data from the Longitudinal Study of Australian Children, a nationally representative cohort that also collects data on the health, psychosocial, and environmental status of parents, and used three multivariate models to assess the impact of psychosocial environmental factors on asthma symptoms at ages 1 year, 4-5 years, and 14-15 years.
• The study population included 3,917 children aged 0-15 years who were sorted into three asthma symptom trajectory groups (low/no asthma, transient high asthma, and persistent high asthma); asthma symptoms were defined as a history of chest wheezing lasting at least a week within the past 12 months.
• The researchers identified several psychosocial environmental factors as exposure variables on the basis of literature reviews; these factors were maternal depression, parents’ financial hardship, parental availability, and parental stressful life events.

TAKEAWAY:

• The mean scores of psychosocial factors for the overall study population remained stable over time, but groups of children exposed to bad trajectories of psychosocial factors were significantly more likely to have transient high and persistent high asthma symptoms.
• In the first year of life, only parents’ stressful life events were significantly associated with the persistent high asthma symptom trajectory group in an adjusted analysis.
• At age 4-5 years, maternal depression, low parental availability, and parents’ stressful life events were significantly associated with persistent high asthma; parents’ financial hardship was significantly associated with transient high asthma symptoms.
• At age 14-15 years, children exposed to “moderate and increasing” maternal depression, “moderate and declining” parents’ financial hardship, and “moderate and increasing” parents’ stressful life events were significantly associated with persistent high asthma versus no or low asthma, with relative risk ratios of 1.55, 1.40, and 1.77, respectively.

IN PRACTICE:

The study findings highlight the need for policy makers to take action to improve asthma control in children by reducing exposure to harmful psychosocial environmental factors, the researchers concluded.

SOURCE:

The lead author of the study was K.M. Shahunja, MBBS, PhD candidate at the University of Queensland, Brisbane, Australia. The study was published online in Pediatric Pulmonology.

LIMITATIONS:

The study is the first known to examine asthma symptom trajectories at different developmental stages, but participant attrition and missing values were limiting factors, as was the inability to account for all potential psychosocial environmental factors that might influence asthma symptoms in childhood.

DISCLOSURES:

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

A version of this article first appeared on Medscape.com.

TOPLINE:

Children with asthma exposed to worsening psychosocial environmental factors during childhood were more likely to have more severe asthma symptoms than those without such exposures.

METHODOLOGY:

• The researchers reviewed data from the Longitudinal Study of Australian Children, a nationally representative cohort that also collects data on the health, psychosocial, and environmental status of parents, and used three multivariate models to assess the impact of psychosocial environmental factors on asthma symptoms at ages 1 year, 4-5 years, and 14-15 years.
• The study population included 3,917 children aged 0-15 years who were sorted into three asthma symptom trajectory groups (low/no asthma, transient high asthma, and persistent high asthma); asthma symptoms were defined as a history of chest wheezing lasting at least a week within the past 12 months.
• The researchers identified several psychosocial environmental factors as exposure variables on the basis of literature reviews; these factors were maternal depression, parents’ financial hardship, parental availability, and parental stressful life events.

TAKEAWAY:

• The mean scores of psychosocial factors for the overall study population remained stable over time, but groups of children exposed to bad trajectories of psychosocial factors were significantly more likely to have transient high and persistent high asthma symptoms.
• In the first year of life, only parents’ stressful life events were significantly associated with the persistent high asthma symptom trajectory group in an adjusted analysis.
• At age 4-5 years, maternal depression, low parental availability, and parents’ stressful life events were significantly associated with persistent high asthma; parents’ financial hardship was significantly associated with transient high asthma symptoms.
• At age 14-15 years, children exposed to “moderate and increasing” maternal depression, “moderate and declining” parents’ financial hardship, and “moderate and increasing” parents’ stressful life events were significantly associated with persistent high asthma versus no or low asthma, with relative risk ratios of 1.55, 1.40, and 1.77, respectively.

IN PRACTICE:

The study findings highlight the need for policy makers to take action to improve asthma control in children by reducing exposure to harmful psychosocial environmental factors, the researchers concluded.

SOURCE:

The lead author of the study was K.M. Shahunja, MBBS, PhD candidate at the University of Queensland, Brisbane, Australia. The study was published online in Pediatric Pulmonology.

LIMITATIONS:

The study is the first known to examine asthma symptom trajectories at different developmental stages, but participant attrition and missing values were limiting factors, as was the inability to account for all potential psychosocial environmental factors that might influence asthma symptoms in childhood.

DISCLOSURES:

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

A version of this article first appeared on Medscape.com.

Use of fluticasone and budesonide for eosinophilic esophagitis during pregnancy had no significant adverse effect on maternal or fetal outcomes, according to new research presented at the annual meeting of the American College of Gastroenterology.

“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”

West Virginia University

In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.

The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.

Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.

Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)

Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.

“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.

Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
 

Pregnant patients can maintain EoE management

“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”

The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.

The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.

However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.

The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.

Use of fluticasone and budesonide for eosinophilic esophagitis during pregnancy had no significant adverse effect on maternal or fetal outcomes, according to new research presented at the annual meeting of the American College of Gastroenterology.

“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”

West Virginia University

In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.

The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.

Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.

Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)

Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.

“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.

Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
 

Pregnant patients can maintain EoE management

“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”

The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.

The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.

However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.

The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.

Use of fluticasone and budesonide for eosinophilic esophagitis during pregnancy had no significant adverse effect on maternal or fetal outcomes, according to new research presented at the annual meeting of the American College of Gastroenterology.

“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”

West Virginia University

In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.

The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.

Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.

Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)

Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.

“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.

Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
 

Pregnant patients can maintain EoE management

“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”

The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.

The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.

However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.

The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.

A novel prognostic tool based on social determinants effectively predicted increased risk of alcohol use relapse in adults who underwent liver transplants for alcoholic liver disease, based on data from 140 individuals.

Alcohol relapse after liver transplant ranges from 4% to as high as 95% among patients with alcoholic liver disease (ALD) and better tools are needed to identify those at increased risk, Jiten P. Kothadia, MD, of the University of Tennessee Health Science Center, Memphis, said in a presentation given in October at the annual meeting of the American College of Gastroenterology.

Dr. Kothadia and colleagues evaluated the effectiveness of the Social Determinant Acuity Tool (S-DAT), which stratified patients in terms of successful post-liver transplant outcomes from excellent (S-DAT scores 0-6) to poor candidates (scores 35-40). The S-DAT categories included cognitive function, mental health, social support, coping skills, financial status, compliance, alcohol abuse, substance abuse, reliability, legal issues, understanding the transplant process, and desire for transplant.

The study population included 140 adults with alcoholic liver disease who underwent a liver transplant between January 2016 and November 2021 at a single center. Before surgery, all patients underwent a thorough psychosocial evaluation using the S-DAT. The mean age of the participants was 53.4 years, 107 were male, and 67.9% had abstained from alcohol for more than 6 months prior to transplant.

The primary outcome of post-liver transplant alcohol relapse was defined as any alcohol use regardless of the amount or frequency, based on patient interviews or blood or urine tests.

Overall, the rate of relapse was 23.6%; and the rate within a year was 18.6%. In a multivariate analysis, S-DAT score was a significant predictor of relapse (odds ratio [OR] 1.65, P = .000). Other independent predictors of relapse were post-LT alcohol treatment (OR 7.11, P = .02), smoking history (OR 0.15, P = .03), and marital status (OR 60.28, P = .000). The area under the receiver operative curves (AUROC) for the S-DAT score to predict alcohol relapse within 1 year after LT was 0.77.

The sensitivity of the S-DAT for predicting relapse risk was 96.2%, and specificity was 40.4%; positive and negative predictive values were 26.9% and 97.9%, respectively.

The high sensitivity and negative predictive values of the S-DAT make it a useful screening tool for identifying patients at low risk of alcohol relapse after a liver transplant, Dr. Kothadia said in an interview. “Our score will guide risk-based interventions post-LT to reduce post-LT relapse and improve long-term outcomes.”

The findings included only data from a single center, which may limit generalizability, Dr. Kothadia said. The tool is not yet clinically available, he noted.

“We would like to perform external validation of our S-DAT score as it stresses the importance of these psychosocial variables,” and to confirm the findings in larger, multicenter, prospective clinical trials, he said.

The study received no outside funding. Dr. Kothadia indicated no relevant financial relationships.

A novel prognostic tool based on social determinants effectively predicted increased risk of alcohol use relapse in adults who underwent liver transplants for alcoholic liver disease, based on data from 140 individuals.

Alcohol relapse after liver transplant ranges from 4% to as high as 95% among patients with alcoholic liver disease (ALD) and better tools are needed to identify those at increased risk, Jiten P. Kothadia, MD, of the University of Tennessee Health Science Center, Memphis, said in a presentation given in October at the annual meeting of the American College of Gastroenterology.

Dr. Kothadia and colleagues evaluated the effectiveness of the Social Determinant Acuity Tool (S-DAT), which stratified patients in terms of successful post-liver transplant outcomes from excellent (S-DAT scores 0-6) to poor candidates (scores 35-40). The S-DAT categories included cognitive function, mental health, social support, coping skills, financial status, compliance, alcohol abuse, substance abuse, reliability, legal issues, understanding the transplant process, and desire for transplant.

The study population included 140 adults with alcoholic liver disease who underwent a liver transplant between January 2016 and November 2021 at a single center. Before surgery, all patients underwent a thorough psychosocial evaluation using the S-DAT. The mean age of the participants was 53.4 years, 107 were male, and 67.9% had abstained from alcohol for more than 6 months prior to transplant.

The primary outcome of post-liver transplant alcohol relapse was defined as any alcohol use regardless of the amount or frequency, based on patient interviews or blood or urine tests.

Overall, the rate of relapse was 23.6%; and the rate within a year was 18.6%. In a multivariate analysis, S-DAT score was a significant predictor of relapse (odds ratio [OR] 1.65, P = .000). Other independent predictors of relapse were post-LT alcohol treatment (OR 7.11, P = .02), smoking history (OR 0.15, P = .03), and marital status (OR 60.28, P = .000). The area under the receiver operative curves (AUROC) for the S-DAT score to predict alcohol relapse within 1 year after LT was 0.77.

The sensitivity of the S-DAT for predicting relapse risk was 96.2%, and specificity was 40.4%; positive and negative predictive values were 26.9% and 97.9%, respectively.

The high sensitivity and negative predictive values of the S-DAT make it a useful screening tool for identifying patients at low risk of alcohol relapse after a liver transplant, Dr. Kothadia said in an interview. “Our score will guide risk-based interventions post-LT to reduce post-LT relapse and improve long-term outcomes.”

The findings included only data from a single center, which may limit generalizability, Dr. Kothadia said. The tool is not yet clinically available, he noted.

“We would like to perform external validation of our S-DAT score as it stresses the importance of these psychosocial variables,” and to confirm the findings in larger, multicenter, prospective clinical trials, he said.

The study received no outside funding. Dr. Kothadia indicated no relevant financial relationships.

A novel prognostic tool based on social determinants effectively predicted increased risk of alcohol use relapse in adults who underwent liver transplants for alcoholic liver disease, based on data from 140 individuals.

Alcohol relapse after liver transplant ranges from 4% to as high as 95% among patients with alcoholic liver disease (ALD) and better tools are needed to identify those at increased risk, Jiten P. Kothadia, MD, of the University of Tennessee Health Science Center, Memphis, said in a presentation given in October at the annual meeting of the American College of Gastroenterology.

Dr. Kothadia and colleagues evaluated the effectiveness of the Social Determinant Acuity Tool (S-DAT), which stratified patients in terms of successful post-liver transplant outcomes from excellent (S-DAT scores 0-6) to poor candidates (scores 35-40). The S-DAT categories included cognitive function, mental health, social support, coping skills, financial status, compliance, alcohol abuse, substance abuse, reliability, legal issues, understanding the transplant process, and desire for transplant.

The study population included 140 adults with alcoholic liver disease who underwent a liver transplant between January 2016 and November 2021 at a single center. Before surgery, all patients underwent a thorough psychosocial evaluation using the S-DAT. The mean age of the participants was 53.4 years, 107 were male, and 67.9% had abstained from alcohol for more than 6 months prior to transplant.

The primary outcome of post-liver transplant alcohol relapse was defined as any alcohol use regardless of the amount or frequency, based on patient interviews or blood or urine tests.

Overall, the rate of relapse was 23.6%; and the rate within a year was 18.6%. In a multivariate analysis, S-DAT score was a significant predictor of relapse (odds ratio [OR] 1.65, P = .000). Other independent predictors of relapse were post-LT alcohol treatment (OR 7.11, P = .02), smoking history (OR 0.15, P = .03), and marital status (OR 60.28, P = .000). The area under the receiver operative curves (AUROC) for the S-DAT score to predict alcohol relapse within 1 year after LT was 0.77.

The sensitivity of the S-DAT for predicting relapse risk was 96.2%, and specificity was 40.4%; positive and negative predictive values were 26.9% and 97.9%, respectively.

The high sensitivity and negative predictive values of the S-DAT make it a useful screening tool for identifying patients at low risk of alcohol relapse after a liver transplant, Dr. Kothadia said in an interview. “Our score will guide risk-based interventions post-LT to reduce post-LT relapse and improve long-term outcomes.”

The findings included only data from a single center, which may limit generalizability, Dr. Kothadia said. The tool is not yet clinically available, he noted.

“We would like to perform external validation of our S-DAT score as it stresses the importance of these psychosocial variables,” and to confirm the findings in larger, multicenter, prospective clinical trials, he said.

The study received no outside funding. Dr. Kothadia indicated no relevant financial relationships.

Two novel devices are similarly effective for tissue approximation of large endoscopic resection defects, but each has advantages, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

“We know from previous data that defect closure is beneficial, and reduces complications such as delayed bleeding and delayed perforation,” said Salmaan A. Jawaid, MD, of Baylor College of Medicine, Houston, in a presentation at the meeting.

Baylor College of Medicine

In the past, defect closure was relatively straightforward; however, “the characteristics of these defects are evolving,” and defects are increasing in size, complexity, and number of locations, he said.

In response, management of resection defects has shifted from a one-step closure to a two-step process with approximation of the widest mucosal edges first, followed by complete resection bed closure, Dr. Jawaid said.

Two novel through the scope (TTS) tissue approximation devices used for the closure of large endoscopic resection defects – the dual-action tissue clip (DAT) and the TTS tack/suture device (TSD) – have not been directly compared on the basis of efficacy and cost, he said.

In the current study, Dr. Jawaid and colleagues randomized 56 adults undergoing tissue approximation and defect closure after endoscopic resection to DAT (31 patients) or TSD (25 patients). The patients were treated at a single center between August 2022 and May 2023 for closures of endoscopic resection defects including gastric, duodenum, and colon lesions greater than 20 mm wide and greater than 30 mm long.

The primary outcomes were technical success of tissue approximation and tissue approximation costs. Secondary outcomes were technical success of complete closure, closure costs, and speed of approximation and closure, as well as safety outcomes. Tissue approximation was defined as less than 15 mm of visible resection bed at the widest margin, and complete closure was defined as no visible resection bed.

Tissue approximation rates were not significantly different between the TSD and DAT groups (88% vs. 83.9%, P = .92). However, approximation cost was significantly lower for DAT compared to TSD ($673.1 vs. $973.6; P = .002).

Similarly, complete closure rates were not significantly different between the TSD and DAT groups (92% vs. 93.5%, P = .83), but closure cost/mm² was significantly lower for DAT compared to TSD ($1.0/mm² vs. $1.6/mm²; P = .002).

Notably, the three DAT failures (60%) underwent successful tissue approximation with TSD, and the single TSD failure (33%) underwent successful tissue approximation using DAT.

In terms of speed, the averages for both tissue approximation time and closure speed were significantly faster in the DAT group, compared with the TSD group (12.2 minutes vs. 4 minutes, P < .0001; 72.7 mm²/min vs. 153.5 mm²/min; P = .003).

“The DAT clip was three times faster than the TSD,” Dr. Jawaid said in his presentation. Adverse events including device-related events, post–electrocautery syndrome, and delayed bleeding were similarly low with both devices. However, the DAT can be less effective in some circumstances, such as a closed space or difficult location. In the cases of duodenal defects, TSD was able to approximate all, but DAT was unable to approximate any. Reasons for DAT clip failure in these cases included the resection bed being too large and tissue tearing upon grasping. In the TSD group, the presence of looping was associated with failures for cecum and colon defects.
 

Data may inform device decisions

“This was an important study conducted to evaluate the different scope devices for defect closure,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and is executive vice chair of internal medicine at the University of Cincinnati.

“These devices have an impact on risk for delayed bleeding and perforation,” said Dr. Afzali, who served as moderator of the session in which the study was presented.

“With different items now available for defect closure, this randomized controlled study provides guidance on which TTS approximation device should be considered, and help determine effectiveness of defect closure,” she said.

“The results of this randomized controlled trial were very informative,” Dr. Afzali said. The data indicated that both DAT and TSD achieved similar rates of tissue approximation and complete closure, but “what was interesting was that one TSD is equivalent to two DAT for tissue approximation. Further, tissue approximation was three times faster with DAT, and complete closure costs were lower in the DAT-treated group.”

In clinical practice, “the study was able to help identify scenarios, such as resection beds involving greater than 50% circumference or defects located in the duodenum, where TSD is preferred over DAT for defect closure. These suggested scenarios are also important for clinical practice and device considerations,” Dr. Afzali said. “Additional studies with use of both devices, TSD and DAT simultaneously on a defect site may be needed to further assist endoscopists in defect management.”

The study was limited by the small size and use of data from a single center.

However, “based on our interim data, both devices are equally effective for tissue approximation of large endoscopic defects,” and facilitate complete defect closure, Dr. Jawaid said.

Ultimately, “both devices have a role,” with DAT being faster and likely more cost effective, while TSD is likely preferable for defects in the duodenum and those with a circumference greater than 50%, he said.

The study received no outside funding. Dr. Jawaid disclosed a consultancy with Boston Scientific, ConMed, CREO Speedboat, and DiLumen. Dr. Afzali disclosed numerous relationships with pharma including having served as an advisor/consultant for AbbVie, Bristol Myers Squibb/Celgene, Eli Lilly, and Gilead, among others.

Two novel devices are similarly effective for tissue approximation of large endoscopic resection defects, but each has advantages, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

“We know from previous data that defect closure is beneficial, and reduces complications such as delayed bleeding and delayed perforation,” said Salmaan A. Jawaid, MD, of Baylor College of Medicine, Houston, in a presentation at the meeting.

Baylor College of Medicine

In the past, defect closure was relatively straightforward; however, “the characteristics of these defects are evolving,” and defects are increasing in size, complexity, and number of locations, he said.

In response, management of resection defects has shifted from a one-step closure to a two-step process with approximation of the widest mucosal edges first, followed by complete resection bed closure, Dr. Jawaid said.

Two novel through the scope (TTS) tissue approximation devices used for the closure of large endoscopic resection defects – the dual-action tissue clip (DAT) and the TTS tack/suture device (TSD) – have not been directly compared on the basis of efficacy and cost, he said.

In the current study, Dr. Jawaid and colleagues randomized 56 adults undergoing tissue approximation and defect closure after endoscopic resection to DAT (31 patients) or TSD (25 patients). The patients were treated at a single center between August 2022 and May 2023 for closures of endoscopic resection defects including gastric, duodenum, and colon lesions greater than 20 mm wide and greater than 30 mm long.

The primary outcomes were technical success of tissue approximation and tissue approximation costs. Secondary outcomes were technical success of complete closure, closure costs, and speed of approximation and closure, as well as safety outcomes. Tissue approximation was defined as less than 15 mm of visible resection bed at the widest margin, and complete closure was defined as no visible resection bed.

Tissue approximation rates were not significantly different between the TSD and DAT groups (88% vs. 83.9%, P = .92). However, approximation cost was significantly lower for DAT compared to TSD ($673.1 vs. $973.6; P = .002).

Similarly, complete closure rates were not significantly different between the TSD and DAT groups (92% vs. 93.5%, P = .83), but closure cost/mm² was significantly lower for DAT compared to TSD ($1.0/mm² vs. $1.6/mm²; P = .002).

Notably, the three DAT failures (60%) underwent successful tissue approximation with TSD, and the single TSD failure (33%) underwent successful tissue approximation using DAT.

In terms of speed, the averages for both tissue approximation time and closure speed were significantly faster in the DAT group, compared with the TSD group (12.2 minutes vs. 4 minutes, P < .0001; 72.7 mm²/min vs. 153.5 mm²/min; P = .003).

“The DAT clip was three times faster than the TSD,” Dr. Jawaid said in his presentation. Adverse events including device-related events, post–electrocautery syndrome, and delayed bleeding were similarly low with both devices. However, the DAT can be less effective in some circumstances, such as a closed space or difficult location. In the cases of duodenal defects, TSD was able to approximate all, but DAT was unable to approximate any. Reasons for DAT clip failure in these cases included the resection bed being too large and tissue tearing upon grasping. In the TSD group, the presence of looping was associated with failures for cecum and colon defects.
 

Data may inform device decisions

“This was an important study conducted to evaluate the different scope devices for defect closure,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and is executive vice chair of internal medicine at the University of Cincinnati.

“These devices have an impact on risk for delayed bleeding and perforation,” said Dr. Afzali, who served as moderator of the session in which the study was presented.

“With different items now available for defect closure, this randomized controlled study provides guidance on which TTS approximation device should be considered, and help determine effectiveness of defect closure,” she said.

“The results of this randomized controlled trial were very informative,” Dr. Afzali said. The data indicated that both DAT and TSD achieved similar rates of tissue approximation and complete closure, but “what was interesting was that one TSD is equivalent to two DAT for tissue approximation. Further, tissue approximation was three times faster with DAT, and complete closure costs were lower in the DAT-treated group.”

In clinical practice, “the study was able to help identify scenarios, such as resection beds involving greater than 50% circumference or defects located in the duodenum, where TSD is preferred over DAT for defect closure. These suggested scenarios are also important for clinical practice and device considerations,” Dr. Afzali said. “Additional studies with use of both devices, TSD and DAT simultaneously on a defect site may be needed to further assist endoscopists in defect management.”

The study was limited by the small size and use of data from a single center.

However, “based on our interim data, both devices are equally effective for tissue approximation of large endoscopic defects,” and facilitate complete defect closure, Dr. Jawaid said.

Ultimately, “both devices have a role,” with DAT being faster and likely more cost effective, while TSD is likely preferable for defects in the duodenum and those with a circumference greater than 50%, he said.

The study received no outside funding. Dr. Jawaid disclosed a consultancy with Boston Scientific, ConMed, CREO Speedboat, and DiLumen. Dr. Afzali disclosed numerous relationships with pharma including having served as an advisor/consultant for AbbVie, Bristol Myers Squibb/Celgene, Eli Lilly, and Gilead, among others.

Two novel devices are similarly effective for tissue approximation of large endoscopic resection defects, but each has advantages, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

“We know from previous data that defect closure is beneficial, and reduces complications such as delayed bleeding and delayed perforation,” said Salmaan A. Jawaid, MD, of Baylor College of Medicine, Houston, in a presentation at the meeting.

Baylor College of Medicine

In the past, defect closure was relatively straightforward; however, “the characteristics of these defects are evolving,” and defects are increasing in size, complexity, and number of locations, he said.

In response, management of resection defects has shifted from a one-step closure to a two-step process with approximation of the widest mucosal edges first, followed by complete resection bed closure, Dr. Jawaid said.

Two novel through the scope (TTS) tissue approximation devices used for the closure of large endoscopic resection defects – the dual-action tissue clip (DAT) and the TTS tack/suture device (TSD) – have not been directly compared on the basis of efficacy and cost, he said.

In the current study, Dr. Jawaid and colleagues randomized 56 adults undergoing tissue approximation and defect closure after endoscopic resection to DAT (31 patients) or TSD (25 patients). The patients were treated at a single center between August 2022 and May 2023 for closures of endoscopic resection defects including gastric, duodenum, and colon lesions greater than 20 mm wide and greater than 30 mm long.

The primary outcomes were technical success of tissue approximation and tissue approximation costs. Secondary outcomes were technical success of complete closure, closure costs, and speed of approximation and closure, as well as safety outcomes. Tissue approximation was defined as less than 15 mm of visible resection bed at the widest margin, and complete closure was defined as no visible resection bed.

Tissue approximation rates were not significantly different between the TSD and DAT groups (88% vs. 83.9%, P = .92). However, approximation cost was significantly lower for DAT compared to TSD ($673.1 vs. $973.6; P = .002).

Similarly, complete closure rates were not significantly different between the TSD and DAT groups (92% vs. 93.5%, P = .83), but closure cost/mm² was significantly lower for DAT compared to TSD ($1.0/mm² vs. $1.6/mm²; P = .002).

Notably, the three DAT failures (60%) underwent successful tissue approximation with TSD, and the single TSD failure (33%) underwent successful tissue approximation using DAT.

In terms of speed, the averages for both tissue approximation time and closure speed were significantly faster in the DAT group, compared with the TSD group (12.2 minutes vs. 4 minutes, P < .0001; 72.7 mm²/min vs. 153.5 mm²/min; P = .003).

“The DAT clip was three times faster than the TSD,” Dr. Jawaid said in his presentation. Adverse events including device-related events, post–electrocautery syndrome, and delayed bleeding were similarly low with both devices. However, the DAT can be less effective in some circumstances, such as a closed space or difficult location. In the cases of duodenal defects, TSD was able to approximate all, but DAT was unable to approximate any. Reasons for DAT clip failure in these cases included the resection bed being too large and tissue tearing upon grasping. In the TSD group, the presence of looping was associated with failures for cecum and colon defects.
 

Data may inform device decisions

“This was an important study conducted to evaluate the different scope devices for defect closure,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and is executive vice chair of internal medicine at the University of Cincinnati.

“These devices have an impact on risk for delayed bleeding and perforation,” said Dr. Afzali, who served as moderator of the session in which the study was presented.

“With different items now available for defect closure, this randomized controlled study provides guidance on which TTS approximation device should be considered, and help determine effectiveness of defect closure,” she said.

“The results of this randomized controlled trial were very informative,” Dr. Afzali said. The data indicated that both DAT and TSD achieved similar rates of tissue approximation and complete closure, but “what was interesting was that one TSD is equivalent to two DAT for tissue approximation. Further, tissue approximation was three times faster with DAT, and complete closure costs were lower in the DAT-treated group.”

In clinical practice, “the study was able to help identify scenarios, such as resection beds involving greater than 50% circumference or defects located in the duodenum, where TSD is preferred over DAT for defect closure. These suggested scenarios are also important for clinical practice and device considerations,” Dr. Afzali said. “Additional studies with use of both devices, TSD and DAT simultaneously on a defect site may be needed to further assist endoscopists in defect management.”

The study was limited by the small size and use of data from a single center.

However, “based on our interim data, both devices are equally effective for tissue approximation of large endoscopic defects,” and facilitate complete defect closure, Dr. Jawaid said.

Ultimately, “both devices have a role,” with DAT being faster and likely more cost effective, while TSD is likely preferable for defects in the duodenum and those with a circumference greater than 50%, he said.

The study received no outside funding. Dr. Jawaid disclosed a consultancy with Boston Scientific, ConMed, CREO Speedboat, and DiLumen. Dr. Afzali disclosed numerous relationships with pharma including having served as an advisor/consultant for AbbVie, Bristol Myers Squibb/Celgene, Eli Lilly, and Gilead, among others.

An intrauterine vacuum-induced hemorrhage control device provided prompt and effective management of bleeding in cases of obstetric hemorrhage, based on data from 800 individuals.

Morbidity and mortality related to postpartum hemorrhage (PPH) are often preventable if caught early, but the persistent rise in PPH-associated morbidity illustrates the need for new and innovative treatments, wrote Dena Goffman, MD, of New York-Presbyterian/Columbia University Irving Medical Center, New York, and colleagues.

New York-Presbyterian/Columbia University Irving Medical Center

The device, known as the Jada System, was cleared by the Food and Drug Administration for management of abnormal postpartum uterine bleeding or postpartum hemorrhage (PPH) in August 2020 and showed safety and effectiveness in a registrational study of 106 patients, the researchers said.

In a postmarket registry medical record review known as RUBY (Treating Abnormal Postpartum Uterine Bleeding or Postpartum Hemorrhage with the Jada System), the researchers examined data collected from Oct. 8, 2020, to March 31, 2022, at 16 centers in the United States. The findings were published in Obstetrics & Gynecology.

The study population included all individuals treated with an intrauterine vacuum-induced hemorrhage control device; of these, 530 were vaginal births and 270 were cesarean births. A total of 94.3% had uterine atony, alone or in conjunction with other causes of bleeding. The median maternal age was 30.3 years; approximately 60% and 53% of patients in the vaginal and cesarean groups were White, and approximately 43% and 49% of patients in the two groups, respectively, were nulliparous.

The median blood loss at the time of device insertion was 1,250 mL in vaginal births and 1,980 mL in cesarean births, and the median time from delivery of the placenta to device insertion was 31 minutes and 108 minutes in the two groups, respectively.

The primary endpoint was treatment success, defined as control of bleeding after device insertion, with no escalation of treatment or recurrence of bleeding after the initial bleeding control and device removal.

Treatment success was achieved in 92.5% of vaginal births and 83.7% of cesarean births, and in 95.8% and 88.2%, respectively, among patients with isolated uterine atony. The median insertion time was 3.1 hours for vaginal births and 4.6 hours for cesarean births.

The safety profile was similar to that in the registrational trial and adverse effects were those expected in patients with PPH, the researchers noted.

A total of 14 SAEs were reported in 13 patients with vaginal births, and 22 SAEs were reported in 21 patients with cesarean births. Of these, three were identified as possibly related to the device or procedure (two cases of endometritis in the vaginal birth group and one case of hemorrhagic shock in the cesarean group); no uterine perforations of deaths were reported during the study.

The study was limited by several factors including the use of data mainly from academic centers, which could limit generalizability, and by the use of a mix of estimated and quantitative reporting of blood loss, the researchers noted. Other limitations include the inability to make direct comparisons to other treatments for PPH.

However, the results confirm the safety and efficacy of the device in a real-world setting and support its use as an important new tool in the management of PPH and reducing maternal morbidity and mortality, they concluded.

Two companies were involved in the study; Alydia Health contributed to the concept, design, and analysis, and Organon contributed to data analysis and reviewed the manuscript.

Dr. Goffman disclosed research support from Organon and Alydia Health, as well as serving as a speaker for Haymarket and PRIME PPH education and for Laborie, participation in the Cooper Surgical Obstetrical Safety Council, and serving as an editor for UpToDate. Several coauthors disclosed relationships with multiple companies including Organon and Alydia Health.

An intrauterine vacuum-induced hemorrhage control device provided prompt and effective management of bleeding in cases of obstetric hemorrhage, based on data from 800 individuals.

Morbidity and mortality related to postpartum hemorrhage (PPH) are often preventable if caught early, but the persistent rise in PPH-associated morbidity illustrates the need for new and innovative treatments, wrote Dena Goffman, MD, of New York-Presbyterian/Columbia University Irving Medical Center, New York, and colleagues.

New York-Presbyterian/Columbia University Irving Medical Center

The device, known as the Jada System, was cleared by the Food and Drug Administration for management of abnormal postpartum uterine bleeding or postpartum hemorrhage (PPH) in August 2020 and showed safety and effectiveness in a registrational study of 106 patients, the researchers said.

In a postmarket registry medical record review known as RUBY (Treating Abnormal Postpartum Uterine Bleeding or Postpartum Hemorrhage with the Jada System), the researchers examined data collected from Oct. 8, 2020, to March 31, 2022, at 16 centers in the United States. The findings were published in Obstetrics & Gynecology.

The study population included all individuals treated with an intrauterine vacuum-induced hemorrhage control device; of these, 530 were vaginal births and 270 were cesarean births. A total of 94.3% had uterine atony, alone or in conjunction with other causes of bleeding. The median maternal age was 30.3 years; approximately 60% and 53% of patients in the vaginal and cesarean groups were White, and approximately 43% and 49% of patients in the two groups, respectively, were nulliparous.

The median blood loss at the time of device insertion was 1,250 mL in vaginal births and 1,980 mL in cesarean births, and the median time from delivery of the placenta to device insertion was 31 minutes and 108 minutes in the two groups, respectively.

The primary endpoint was treatment success, defined as control of bleeding after device insertion, with no escalation of treatment or recurrence of bleeding after the initial bleeding control and device removal.

Treatment success was achieved in 92.5% of vaginal births and 83.7% of cesarean births, and in 95.8% and 88.2%, respectively, among patients with isolated uterine atony. The median insertion time was 3.1 hours for vaginal births and 4.6 hours for cesarean births.

The safety profile was similar to that in the registrational trial and adverse effects were those expected in patients with PPH, the researchers noted.

A total of 14 SAEs were reported in 13 patients with vaginal births, and 22 SAEs were reported in 21 patients with cesarean births. Of these, three were identified as possibly related to the device or procedure (two cases of endometritis in the vaginal birth group and one case of hemorrhagic shock in the cesarean group); no uterine perforations of deaths were reported during the study.

The study was limited by several factors including the use of data mainly from academic centers, which could limit generalizability, and by the use of a mix of estimated and quantitative reporting of blood loss, the researchers noted. Other limitations include the inability to make direct comparisons to other treatments for PPH.

However, the results confirm the safety and efficacy of the device in a real-world setting and support its use as an important new tool in the management of PPH and reducing maternal morbidity and mortality, they concluded.

Two companies were involved in the study; Alydia Health contributed to the concept, design, and analysis, and Organon contributed to data analysis and reviewed the manuscript.

Dr. Goffman disclosed research support from Organon and Alydia Health, as well as serving as a speaker for Haymarket and PRIME PPH education and for Laborie, participation in the Cooper Surgical Obstetrical Safety Council, and serving as an editor for UpToDate. Several coauthors disclosed relationships with multiple companies including Organon and Alydia Health.

An intrauterine vacuum-induced hemorrhage control device provided prompt and effective management of bleeding in cases of obstetric hemorrhage, based on data from 800 individuals.

Morbidity and mortality related to postpartum hemorrhage (PPH) are often preventable if caught early, but the persistent rise in PPH-associated morbidity illustrates the need for new and innovative treatments, wrote Dena Goffman, MD, of New York-Presbyterian/Columbia University Irving Medical Center, New York, and colleagues.

New York-Presbyterian/Columbia University Irving Medical Center

The device, known as the Jada System, was cleared by the Food and Drug Administration for management of abnormal postpartum uterine bleeding or postpartum hemorrhage (PPH) in August 2020 and showed safety and effectiveness in a registrational study of 106 patients, the researchers said.

In a postmarket registry medical record review known as RUBY (Treating Abnormal Postpartum Uterine Bleeding or Postpartum Hemorrhage with the Jada System), the researchers examined data collected from Oct. 8, 2020, to March 31, 2022, at 16 centers in the United States. The findings were published in Obstetrics & Gynecology.

The study population included all individuals treated with an intrauterine vacuum-induced hemorrhage control device; of these, 530 were vaginal births and 270 were cesarean births. A total of 94.3% had uterine atony, alone or in conjunction with other causes of bleeding. The median maternal age was 30.3 years; approximately 60% and 53% of patients in the vaginal and cesarean groups were White, and approximately 43% and 49% of patients in the two groups, respectively, were nulliparous.

The median blood loss at the time of device insertion was 1,250 mL in vaginal births and 1,980 mL in cesarean births, and the median time from delivery of the placenta to device insertion was 31 minutes and 108 minutes in the two groups, respectively.

The primary endpoint was treatment success, defined as control of bleeding after device insertion, with no escalation of treatment or recurrence of bleeding after the initial bleeding control and device removal.

Treatment success was achieved in 92.5% of vaginal births and 83.7% of cesarean births, and in 95.8% and 88.2%, respectively, among patients with isolated uterine atony. The median insertion time was 3.1 hours for vaginal births and 4.6 hours for cesarean births.

The safety profile was similar to that in the registrational trial and adverse effects were those expected in patients with PPH, the researchers noted.

A total of 14 SAEs were reported in 13 patients with vaginal births, and 22 SAEs were reported in 21 patients with cesarean births. Of these, three were identified as possibly related to the device or procedure (two cases of endometritis in the vaginal birth group and one case of hemorrhagic shock in the cesarean group); no uterine perforations of deaths were reported during the study.

The study was limited by several factors including the use of data mainly from academic centers, which could limit generalizability, and by the use of a mix of estimated and quantitative reporting of blood loss, the researchers noted. Other limitations include the inability to make direct comparisons to other treatments for PPH.

However, the results confirm the safety and efficacy of the device in a real-world setting and support its use as an important new tool in the management of PPH and reducing maternal morbidity and mortality, they concluded.

Two companies were involved in the study; Alydia Health contributed to the concept, design, and analysis, and Organon contributed to data analysis and reviewed the manuscript.

Dr. Goffman disclosed research support from Organon and Alydia Health, as well as serving as a speaker for Haymarket and PRIME PPH education and for Laborie, participation in the Cooper Surgical Obstetrical Safety Council, and serving as an editor for UpToDate. Several coauthors disclosed relationships with multiple companies including Organon and Alydia Health.

TOPLINE:

An international expert consensus offers guidance to diagnose, assess, and treat adult patients experiencing drug reaction with eosinophilia and systemic symptoms (DRESS).

METHODOLOGY:

Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.

To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.

An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.

After revisions and the second round, the group reached consensus for 93 statements overall.

TAKEAWAY:

The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.

The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.

Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.

IN PRACTICE:

“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”

SOURCE:

The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.

LIMITATIONS:

Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.

DISCLOSURES:

The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.

A version of this article appeared on Medscape.com.

TOPLINE:

An international expert consensus offers guidance to diagnose, assess, and treat adult patients experiencing drug reaction with eosinophilia and systemic symptoms (DRESS).

METHODOLOGY:

Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.

To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.

An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.

After revisions and the second round, the group reached consensus for 93 statements overall.

TAKEAWAY:

The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.

The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.

Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.

IN PRACTICE:

“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”

SOURCE:

The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.

LIMITATIONS:

Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.

DISCLOSURES:

The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.

A version of this article appeared on Medscape.com.

TOPLINE:

An international expert consensus offers guidance to diagnose, assess, and treat adult patients experiencing drug reaction with eosinophilia and systemic symptoms (DRESS).

METHODOLOGY:

Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.

To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.

An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.

After revisions and the second round, the group reached consensus for 93 statements overall.

TAKEAWAY:

The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.

The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.

Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.

IN PRACTICE:

“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”

SOURCE:

The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.

LIMITATIONS:

Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.

DISCLOSURES:

The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.

A version of this article appeared on Medscape.com.

A combination oral-only therapy of bedaquiline, pretomanid, and linezolid was significantly more effective than standard care in preventing unfavorable outcomes in patients with treatment-resistant tuberculosis, based on data from more than 500 individuals.

Rifampin-resistant tuberculosis affects approximately 500,000 people worldwide each year, but current treatments are associated with toxicity and limited effectiveness, and data on the use of new and repurposed drug combinations are lacking, wrote Bern-Thomas Nyang’wa, MBBS, of Médecins Sans Frontières, Amsterdam, and colleagues.

In a study known as the TB-PRACTECAL trial, the researchers enrolled 552 pulmonary rifampin-resistant tuberculosis patients aged 15 years and older to examine several new and repurposed drug combinations. The participants were randomized in a 1:1:1:1 ratio to treatment with 36-80 weeks of standard care; 24-week oral bedaquiline, pretomanid, and linezolid (BPaL); BPaL plus clofazimine (BPaLC); or BPaL plus moxifloxacin (BPaLM) . This was followed by stage two of the trial, in which participants were randomized 1:1 to receive standard care or BPaLM. The current study, published in The Lancet Respiratory Medicine, reported the stage two findings; the primary outcome was a composite of unfavorable outcomes at 72 weeks including death, treatment failure, treatment discontinuation, recurrence of tuberculosis, or loss to follow-up.

The modified intent-to-treat population included 138 patients in the BPaLM group and 137 patients in the standard care group. In this population, 56 (41%) of 137 participants in the standard care group and 16 (12%) of 137 participants in the BPaLM group met criteria for the unfavorable outcome at 72 weeks; noninferiority and superiority were significantly greater in the BPaLM group (P < .0001).

Early discontinuation was the main reason patients met the unfavorable outcome criteria (89% of standard care patients and 69% of BPaLM patients); adverse events accounted for 23% of discontinuations in the standard care group and 64% of discontinuations in the BPaLM group.

However, fewer patients in the BPaLM group experienced grade 3 or higher adverse events compared with the standard care group (23% vs. 48%). The most common adverse events included hepatic disorders, cardiac disorders, and anemia.

In addition, all subgroup analyses favored BPaLM over standard care at 72 weeks including subgroups based on sex, age, disease severity, re-treatment status, and smoking status.

The findings were limited by several factors including the changes to standard of care over the course of the study, potential bias because the study was stopped for efficacy, and inclusion of loss to follow-up as part of the composite unfavorable outcome, the researchers noted.

Remaining research questions include the optimal dose of linezolid, whether use of alternative fluoroquinolones would yield similar results, and whether the results would generalize to populations including children, pregnant women, and patients with extrapulmonary tuberculosis, they added.

However, the results support BPaLM as the preferred treatment for adults and adolescents with pulmonary rifampin-resistant TB, the researchers concluded.
 

BPaLM poised to improve TB care

Before 2020, treatment for rifampin-resistant tuberculosis was 9-20 months in duration, toxic, and inadequately effective, and new treatment regimens are urgently needed, Mary Jo Farmer, MD, a pulmonary and critical care specialist at the University of Massachusetts Baystate Health Regional Campus, Springfield, said in an interview.

“The BPaL-based regimens perform better than the 9- to 20-month standard of care, are shorter in duration, have a lower pill burden, improve quality of life, and are cost-effective,” she said. “The BPaL regimens have the potential to improve outcomes for thousands of patients with rifampin-resistant tuberculosis.”

“The 24-week oral regimen consisting of bedaquiline, pretomanid, linezolid and moxifloxacin is noninferior to standard of care for treatment of patients with pulmonary rifampin-resistant tuberculosis, and this BPaLM regimen was added to the WHO guidance for treatment of this condition in 2022,” said Dr. Farmer, who was not involved in the study. “It remains to be seen if BPaLM will become the preferred regimen for adolescents and adults with pulmonary rifampin-resistant tuberculosis,” she said.

Dr. Farmer agreed with the study authors that the optimal dose of linezolid, optimal duration of treatment, and the role of dose reduction remain unknown, and pharmacokinetic studies are needed to identify these parameters. 

The study was supported by Médecins Sans Frontières. TB Alliance donated pretomanid to the study prior to its commercialization. The researchers had no financial conflicts to disclose. Dr. Farmer had no financial conflicts to disclose, but serves on the editorial advisory board of CHEST Physician.

A combination oral-only therapy of bedaquiline, pretomanid, and linezolid was significantly more effective than standard care in preventing unfavorable outcomes in patients with treatment-resistant tuberculosis, based on data from more than 500 individuals.

Rifampin-resistant tuberculosis affects approximately 500,000 people worldwide each year, but current treatments are associated with toxicity and limited effectiveness, and data on the use of new and repurposed drug combinations are lacking, wrote Bern-Thomas Nyang’wa, MBBS, of Médecins Sans Frontières, Amsterdam, and colleagues.

In a study known as the TB-PRACTECAL trial, the researchers enrolled 552 pulmonary rifampin-resistant tuberculosis patients aged 15 years and older to examine several new and repurposed drug combinations. The participants were randomized in a 1:1:1:1 ratio to treatment with 36-80 weeks of standard care; 24-week oral bedaquiline, pretomanid, and linezolid (BPaL); BPaL plus clofazimine (BPaLC); or BPaL plus moxifloxacin (BPaLM) . This was followed by stage two of the trial, in which participants were randomized 1:1 to receive standard care or BPaLM. The current study, published in The Lancet Respiratory Medicine, reported the stage two findings; the primary outcome was a composite of unfavorable outcomes at 72 weeks including death, treatment failure, treatment discontinuation, recurrence of tuberculosis, or loss to follow-up.

The modified intent-to-treat population included 138 patients in the BPaLM group and 137 patients in the standard care group. In this population, 56 (41%) of 137 participants in the standard care group and 16 (12%) of 137 participants in the BPaLM group met criteria for the unfavorable outcome at 72 weeks; noninferiority and superiority were significantly greater in the BPaLM group (P < .0001).

Early discontinuation was the main reason patients met the unfavorable outcome criteria (89% of standard care patients and 69% of BPaLM patients); adverse events accounted for 23% of discontinuations in the standard care group and 64% of discontinuations in the BPaLM group.

However, fewer patients in the BPaLM group experienced grade 3 or higher adverse events compared with the standard care group (23% vs. 48%). The most common adverse events included hepatic disorders, cardiac disorders, and anemia.

In addition, all subgroup analyses favored BPaLM over standard care at 72 weeks including subgroups based on sex, age, disease severity, re-treatment status, and smoking status.

The findings were limited by several factors including the changes to standard of care over the course of the study, potential bias because the study was stopped for efficacy, and inclusion of loss to follow-up as part of the composite unfavorable outcome, the researchers noted.

Remaining research questions include the optimal dose of linezolid, whether use of alternative fluoroquinolones would yield similar results, and whether the results would generalize to populations including children, pregnant women, and patients with extrapulmonary tuberculosis, they added.

However, the results support BPaLM as the preferred treatment for adults and adolescents with pulmonary rifampin-resistant TB, the researchers concluded.
 

BPaLM poised to improve TB care

Before 2020, treatment for rifampin-resistant tuberculosis was 9-20 months in duration, toxic, and inadequately effective, and new treatment regimens are urgently needed, Mary Jo Farmer, MD, a pulmonary and critical care specialist at the University of Massachusetts Baystate Health Regional Campus, Springfield, said in an interview.

“The BPaL-based regimens perform better than the 9- to 20-month standard of care, are shorter in duration, have a lower pill burden, improve quality of life, and are cost-effective,” she said. “The BPaL regimens have the potential to improve outcomes for thousands of patients with rifampin-resistant tuberculosis.”

“The 24-week oral regimen consisting of bedaquiline, pretomanid, linezolid and moxifloxacin is noninferior to standard of care for treatment of patients with pulmonary rifampin-resistant tuberculosis, and this BPaLM regimen was added to the WHO guidance for treatment of this condition in 2022,” said Dr. Farmer, who was not involved in the study. “It remains to be seen if BPaLM will become the preferred regimen for adolescents and adults with pulmonary rifampin-resistant tuberculosis,” she said.

Dr. Farmer agreed with the study authors that the optimal dose of linezolid, optimal duration of treatment, and the role of dose reduction remain unknown, and pharmacokinetic studies are needed to identify these parameters. 

The study was supported by Médecins Sans Frontières. TB Alliance donated pretomanid to the study prior to its commercialization. The researchers had no financial conflicts to disclose. Dr. Farmer had no financial conflicts to disclose, but serves on the editorial advisory board of CHEST Physician.

A combination oral-only therapy of bedaquiline, pretomanid, and linezolid was significantly more effective than standard care in preventing unfavorable outcomes in patients with treatment-resistant tuberculosis, based on data from more than 500 individuals.

Rifampin-resistant tuberculosis affects approximately 500,000 people worldwide each year, but current treatments are associated with toxicity and limited effectiveness, and data on the use of new and repurposed drug combinations are lacking, wrote Bern-Thomas Nyang’wa, MBBS, of Médecins Sans Frontières, Amsterdam, and colleagues.

In a study known as the TB-PRACTECAL trial, the researchers enrolled 552 pulmonary rifampin-resistant tuberculosis patients aged 15 years and older to examine several new and repurposed drug combinations. The participants were randomized in a 1:1:1:1 ratio to treatment with 36-80 weeks of standard care; 24-week oral bedaquiline, pretomanid, and linezolid (BPaL); BPaL plus clofazimine (BPaLC); or BPaL plus moxifloxacin (BPaLM) . This was followed by stage two of the trial, in which participants were randomized 1:1 to receive standard care or BPaLM. The current study, published in The Lancet Respiratory Medicine, reported the stage two findings; the primary outcome was a composite of unfavorable outcomes at 72 weeks including death, treatment failure, treatment discontinuation, recurrence of tuberculosis, or loss to follow-up.

The modified intent-to-treat population included 138 patients in the BPaLM group and 137 patients in the standard care group. In this population, 56 (41%) of 137 participants in the standard care group and 16 (12%) of 137 participants in the BPaLM group met criteria for the unfavorable outcome at 72 weeks; noninferiority and superiority were significantly greater in the BPaLM group (P < .0001).

Early discontinuation was the main reason patients met the unfavorable outcome criteria (89% of standard care patients and 69% of BPaLM patients); adverse events accounted for 23% of discontinuations in the standard care group and 64% of discontinuations in the BPaLM group.

However, fewer patients in the BPaLM group experienced grade 3 or higher adverse events compared with the standard care group (23% vs. 48%). The most common adverse events included hepatic disorders, cardiac disorders, and anemia.

In addition, all subgroup analyses favored BPaLM over standard care at 72 weeks including subgroups based on sex, age, disease severity, re-treatment status, and smoking status.

The findings were limited by several factors including the changes to standard of care over the course of the study, potential bias because the study was stopped for efficacy, and inclusion of loss to follow-up as part of the composite unfavorable outcome, the researchers noted.

Remaining research questions include the optimal dose of linezolid, whether use of alternative fluoroquinolones would yield similar results, and whether the results would generalize to populations including children, pregnant women, and patients with extrapulmonary tuberculosis, they added.

However, the results support BPaLM as the preferred treatment for adults and adolescents with pulmonary rifampin-resistant TB, the researchers concluded.
 

BPaLM poised to improve TB care

Before 2020, treatment for rifampin-resistant tuberculosis was 9-20 months in duration, toxic, and inadequately effective, and new treatment regimens are urgently needed, Mary Jo Farmer, MD, a pulmonary and critical care specialist at the University of Massachusetts Baystate Health Regional Campus, Springfield, said in an interview.

“The BPaL-based regimens perform better than the 9- to 20-month standard of care, are shorter in duration, have a lower pill burden, improve quality of life, and are cost-effective,” she said. “The BPaL regimens have the potential to improve outcomes for thousands of patients with rifampin-resistant tuberculosis.”

“The 24-week oral regimen consisting of bedaquiline, pretomanid, linezolid and moxifloxacin is noninferior to standard of care for treatment of patients with pulmonary rifampin-resistant tuberculosis, and this BPaLM regimen was added to the WHO guidance for treatment of this condition in 2022,” said Dr. Farmer, who was not involved in the study. “It remains to be seen if BPaLM will become the preferred regimen for adolescents and adults with pulmonary rifampin-resistant tuberculosis,” she said.

Dr. Farmer agreed with the study authors that the optimal dose of linezolid, optimal duration of treatment, and the role of dose reduction remain unknown, and pharmacokinetic studies are needed to identify these parameters. 

The study was supported by Médecins Sans Frontières. TB Alliance donated pretomanid to the study prior to its commercialization. The researchers had no financial conflicts to disclose. Dr. Farmer had no financial conflicts to disclose, but serves on the editorial advisory board of CHEST Physician.