Key clinical point: Galcanezumab significantly reduced interictal burden, as measured by the 4-item Migraine Interictal Burden Scale (MIBS-4), in patients with episodic or chronic migraine and multiple prior migraine preventive treatment failures.

Major finding: At 3 months, the mean MIBS-4 score reduced significantly with galcanezumab vs placebo in the overall population (least-squares mean change [Δ] −1.9 vs −0.8; P < .0001) and in patients with episodic (Δ −1.8 vs −1.1; P = .033) and chronic (Δ −1.8 vs −0.3; P < .001) migraine.

Study details: This was a post hoc analysis of the CONQUER study including 462 patients with chronic or episodic migraine and multiple prior migraine preventive treatment failures who were randomly assigned to receive galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving research funding or support from various pharmaceutical sources, including Eli Lilly and Company. Some others declared being employees and minor stockholders of Eli Lilly and Company.

Source: Lipton RB et al. Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study. Headache. 2023 (Feb 16). Doi: 10.1111/head.14460

Key clinical point: Galcanezumab significantly reduced interictal burden, as measured by the 4-item Migraine Interictal Burden Scale (MIBS-4), in patients with episodic or chronic migraine and multiple prior migraine preventive treatment failures.

Major finding: At 3 months, the mean MIBS-4 score reduced significantly with galcanezumab vs placebo in the overall population (least-squares mean change [Δ] −1.9 vs −0.8; P < .0001) and in patients with episodic (Δ −1.8 vs −1.1; P = .033) and chronic (Δ −1.8 vs −0.3; P < .001) migraine.

Study details: This was a post hoc analysis of the CONQUER study including 462 patients with chronic or episodic migraine and multiple prior migraine preventive treatment failures who were randomly assigned to receive galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving research funding or support from various pharmaceutical sources, including Eli Lilly and Company. Some others declared being employees and minor stockholders of Eli Lilly and Company.

Source: Lipton RB et al. Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study. Headache. 2023 (Feb 16). Doi: 10.1111/head.14460

Key clinical point: Galcanezumab significantly reduced interictal burden, as measured by the 4-item Migraine Interictal Burden Scale (MIBS-4), in patients with episodic or chronic migraine and multiple prior migraine preventive treatment failures.

Major finding: At 3 months, the mean MIBS-4 score reduced significantly with galcanezumab vs placebo in the overall population (least-squares mean change [Δ] −1.9 vs −0.8; P < .0001) and in patients with episodic (Δ −1.8 vs −1.1; P = .033) and chronic (Δ −1.8 vs −0.3; P < .001) migraine.

Study details: This was a post hoc analysis of the CONQUER study including 462 patients with chronic or episodic migraine and multiple prior migraine preventive treatment failures who were randomly assigned to receive galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving research funding or support from various pharmaceutical sources, including Eli Lilly and Company. Some others declared being employees and minor stockholders of Eli Lilly and Company.

Source: Lipton RB et al. Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study. Headache. 2023 (Feb 16). Doi: 10.1111/head.14460

Key clinical point: Network meta-analysis confirms the overall safety of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and gepants for migraine prevention, with rare instances of treatment discontinuation.

Major finding: The risk for serious adverse events was not significantly different with active treatments and placebo, with 30 mg eptinezumab being the only treatment significantly associated with higher odds of adverse events leading to treatment discontinuation (odds ratio [OR] 2.62; 95% CI 1.03-6.66). Compared with placebo, the risk for treatment-emergent adverse events was not significantly different with 30 mg and 100 mg eptinezumab and was the highest with 240 mg galcanezumab (OR 1.63; 95% CI 1.33-2.00) and 120 mg galcanezumab (OR 1.40; 95% CI 1.16-1.70), with the most frequent being injection site erythema, induration, and pruritus.

Study details: The data come from a network meta-analysis of 19 phase 3 randomized controlled trials including 14,584 patients with migraine.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Messina R et al. Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis. Cephalalgia. 2023;43(3):3331024231152169 (Feb 14). Doi: 10.1177/03331024231152169

Key clinical point: Network meta-analysis confirms the overall safety of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and gepants for migraine prevention, with rare instances of treatment discontinuation.

Major finding: The risk for serious adverse events was not significantly different with active treatments and placebo, with 30 mg eptinezumab being the only treatment significantly associated with higher odds of adverse events leading to treatment discontinuation (odds ratio [OR] 2.62; 95% CI 1.03-6.66). Compared with placebo, the risk for treatment-emergent adverse events was not significantly different with 30 mg and 100 mg eptinezumab and was the highest with 240 mg galcanezumab (OR 1.63; 95% CI 1.33-2.00) and 120 mg galcanezumab (OR 1.40; 95% CI 1.16-1.70), with the most frequent being injection site erythema, induration, and pruritus.

Study details: The data come from a network meta-analysis of 19 phase 3 randomized controlled trials including 14,584 patients with migraine.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Messina R et al. Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis. Cephalalgia. 2023;43(3):3331024231152169 (Feb 14). Doi: 10.1177/03331024231152169

Key clinical point: Network meta-analysis confirms the overall safety of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies and gepants for migraine prevention, with rare instances of treatment discontinuation.

Major finding: The risk for serious adverse events was not significantly different with active treatments and placebo, with 30 mg eptinezumab being the only treatment significantly associated with higher odds of adverse events leading to treatment discontinuation (odds ratio [OR] 2.62; 95% CI 1.03-6.66). Compared with placebo, the risk for treatment-emergent adverse events was not significantly different with 30 mg and 100 mg eptinezumab and was the highest with 240 mg galcanezumab (OR 1.63; 95% CI 1.33-2.00) and 120 mg galcanezumab (OR 1.40; 95% CI 1.16-1.70), with the most frequent being injection site erythema, induration, and pruritus.

Study details: The data come from a network meta-analysis of 19 phase 3 randomized controlled trials including 14,584 patients with migraine.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Messina R et al. Safety and tolerability of monoclonal antibodies targeting the CGRP pathway and gepants in migraine prevention: A systematic review and network meta-analysis. Cephalalgia. 2023;43(3):3331024231152169 (Feb 14). Doi: 10.1177/03331024231152169

It’s estimated that half of all people in the world are infected with Helicobacter pylori, a bacterium associated with increased risk for gastric ulcers and gastric cancer.

However, only a small percentage of people with H. pylori infection will go on to develop gastric cancer.

Now a team from Japan reports that specific mutations in genes associated with DNA repair, when combined with the common bacterial infection H. pylori, appear to significantly increase the risk for gastric cancer.

The new findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed, say editorialists commenting on the study.

The article and accompanying editorial were published in The New England Journal of Medicine.

For this study, Yoshiaki Usui, MD, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and colleagues analyzed samples from 10,426 patients with gastric cancer as well as 38,153 control samples from a Japanese biobank.

First, they looked at the association between gastric cancer and germline pathogenic variants in 27 genes known to predispose carriers to cancers.

They also looked at the combined effects of pathogenic variants and H. pylori infection and calculated the cumulative risk among 1,433 patients with gastric cancer and 5,997 control samples from a cancer-center research database.

They found that germline pathogenic variants in nine genes were associated with the risk for gastric cancer. The genes were APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2.

The pathogenic germline (inherited) variants in these nine genes were associated with homologous recombination, which involves an exchange of nucleotide sequences between two similar or identical DNA molecules that occurs during meiosis and during repair of double-strand DNA breaks.

The investigators calculated that the cumulative risk for gastric cancer at age 85 among carriers of the variants who were infected with H. pylori was 45.5%, compared with 14.4% for control persons who were infected but were not carriers of the germline pathogenic variants.

The risk for gastric cancer was less than 5% among those without H. pylori infections, regardless of their carrier status.

“Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important,” Dr. Usui and colleagues wrote.

“It is remarkable that pathogenic variants in homologous-recombination genes drive tumorigenesis only in the context of H. pylori infection,” Anne Müller, PhD, and Jiazhuo He, MD, of the University of Zürich, wrote in the accompanying editorial.

“This observation has numerous implications, not only for the diagnosis, prevention, and possibly treatment of the fraction of cases of gastric cancer with pathogenic gene variants that arise due to H. pylori infection but also for a better understanding of the biology of other cancers arising on a background of homologous-recombination deficiency. It is quite conceivable that other DNA-damaging environmental factors contributing to human carcinogenesis have been overlooked.” they wrote.

The study was supported by grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Science, Sports, Culture, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; and the Australian National Health and Medical Research Council. Dr. Usui, Dr. Müller, and Dr. He have disclosed no relevant financial relationships.
 

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

It’s estimated that half of all people in the world are infected with Helicobacter pylori, a bacterium associated with increased risk for gastric ulcers and gastric cancer.

However, only a small percentage of people with H. pylori infection will go on to develop gastric cancer.

Now a team from Japan reports that specific mutations in genes associated with DNA repair, when combined with the common bacterial infection H. pylori, appear to significantly increase the risk for gastric cancer.

The new findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed, say editorialists commenting on the study.

The article and accompanying editorial were published in The New England Journal of Medicine.

For this study, Yoshiaki Usui, MD, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and colleagues analyzed samples from 10,426 patients with gastric cancer as well as 38,153 control samples from a Japanese biobank.

First, they looked at the association between gastric cancer and germline pathogenic variants in 27 genes known to predispose carriers to cancers.

They also looked at the combined effects of pathogenic variants and H. pylori infection and calculated the cumulative risk among 1,433 patients with gastric cancer and 5,997 control samples from a cancer-center research database.

They found that germline pathogenic variants in nine genes were associated with the risk for gastric cancer. The genes were APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2.

The pathogenic germline (inherited) variants in these nine genes were associated with homologous recombination, which involves an exchange of nucleotide sequences between two similar or identical DNA molecules that occurs during meiosis and during repair of double-strand DNA breaks.

The investigators calculated that the cumulative risk for gastric cancer at age 85 among carriers of the variants who were infected with H. pylori was 45.5%, compared with 14.4% for control persons who were infected but were not carriers of the germline pathogenic variants.

The risk for gastric cancer was less than 5% among those without H. pylori infections, regardless of their carrier status.

“Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important,” Dr. Usui and colleagues wrote.

“It is remarkable that pathogenic variants in homologous-recombination genes drive tumorigenesis only in the context of H. pylori infection,” Anne Müller, PhD, and Jiazhuo He, MD, of the University of Zürich, wrote in the accompanying editorial.

“This observation has numerous implications, not only for the diagnosis, prevention, and possibly treatment of the fraction of cases of gastric cancer with pathogenic gene variants that arise due to H. pylori infection but also for a better understanding of the biology of other cancers arising on a background of homologous-recombination deficiency. It is quite conceivable that other DNA-damaging environmental factors contributing to human carcinogenesis have been overlooked.” they wrote.

The study was supported by grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Science, Sports, Culture, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; and the Australian National Health and Medical Research Council. Dr. Usui, Dr. Müller, and Dr. He have disclosed no relevant financial relationships.
 

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

It’s estimated that half of all people in the world are infected with Helicobacter pylori, a bacterium associated with increased risk for gastric ulcers and gastric cancer.

However, only a small percentage of people with H. pylori infection will go on to develop gastric cancer.

Now a team from Japan reports that specific mutations in genes associated with DNA repair, when combined with the common bacterial infection H. pylori, appear to significantly increase the risk for gastric cancer.

The new findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed, say editorialists commenting on the study.

The article and accompanying editorial were published in The New England Journal of Medicine.

For this study, Yoshiaki Usui, MD, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and colleagues analyzed samples from 10,426 patients with gastric cancer as well as 38,153 control samples from a Japanese biobank.

First, they looked at the association between gastric cancer and germline pathogenic variants in 27 genes known to predispose carriers to cancers.

They also looked at the combined effects of pathogenic variants and H. pylori infection and calculated the cumulative risk among 1,433 patients with gastric cancer and 5,997 control samples from a cancer-center research database.

They found that germline pathogenic variants in nine genes were associated with the risk for gastric cancer. The genes were APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2.

The pathogenic germline (inherited) variants in these nine genes were associated with homologous recombination, which involves an exchange of nucleotide sequences between two similar or identical DNA molecules that occurs during meiosis and during repair of double-strand DNA breaks.

The investigators calculated that the cumulative risk for gastric cancer at age 85 among carriers of the variants who were infected with H. pylori was 45.5%, compared with 14.4% for control persons who were infected but were not carriers of the germline pathogenic variants.

The risk for gastric cancer was less than 5% among those without H. pylori infections, regardless of their carrier status.

“Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important,” Dr. Usui and colleagues wrote.

“It is remarkable that pathogenic variants in homologous-recombination genes drive tumorigenesis only in the context of H. pylori infection,” Anne Müller, PhD, and Jiazhuo He, MD, of the University of Zürich, wrote in the accompanying editorial.

“This observation has numerous implications, not only for the diagnosis, prevention, and possibly treatment of the fraction of cases of gastric cancer with pathogenic gene variants that arise due to H. pylori infection but also for a better understanding of the biology of other cancers arising on a background of homologous-recombination deficiency. It is quite conceivable that other DNA-damaging environmental factors contributing to human carcinogenesis have been overlooked.” they wrote.

The study was supported by grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Science, Sports, Culture, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; and the Australian National Health and Medical Research Council. Dr. Usui, Dr. Müller, and Dr. He have disclosed no relevant financial relationships.
 

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

Key clinical point: Zavegepant nasal spray was effective in the acute treatment of migraine, with favorable tolerability and safety profiles.

Major finding: At 2 hours post-dose, higher proportions of patients treated with zavegepant vs placebo were free from pain (risk difference 8.8 percentage points; P < .0001) and from their most bothersome symptom (risk difference 8.7 percentage points; P = .0012). Dysgeusia (21% vs 5%), nasal discomfort (4% vs 1%), and nausea (3% vs 1%) were the most common adverse events in the zavegepant vs placebo group.

Study details: Findings are from a phase 3 trial including 1405 patients with ≥1-year history of migraine with or without aura who were randomly assigned to receive zavegepant 10 mg nasal spray (n = 703) or matching placebo (n = 702).

Disclosures: This study was funded by Biohaven Pharmaceuticals. Some authors declared being employees of and holding stocks or stock options in Biohaven Pharmaceuticals. Some others declared ties with various sources, including Biohaven Pharmaceuticals.

Source: Lipton RB et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: A phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol. 2023;22(3):209-217 (Mar). Doi: 10.1016/S1474-4422(22)00517-8

Key clinical point: Zavegepant nasal spray was effective in the acute treatment of migraine, with favorable tolerability and safety profiles.

Major finding: At 2 hours post-dose, higher proportions of patients treated with zavegepant vs placebo were free from pain (risk difference 8.8 percentage points; P < .0001) and from their most bothersome symptom (risk difference 8.7 percentage points; P = .0012). Dysgeusia (21% vs 5%), nasal discomfort (4% vs 1%), and nausea (3% vs 1%) were the most common adverse events in the zavegepant vs placebo group.

Study details: Findings are from a phase 3 trial including 1405 patients with ≥1-year history of migraine with or without aura who were randomly assigned to receive zavegepant 10 mg nasal spray (n = 703) or matching placebo (n = 702).

Disclosures: This study was funded by Biohaven Pharmaceuticals. Some authors declared being employees of and holding stocks or stock options in Biohaven Pharmaceuticals. Some others declared ties with various sources, including Biohaven Pharmaceuticals.

Source: Lipton RB et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: A phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol. 2023;22(3):209-217 (Mar). Doi: 10.1016/S1474-4422(22)00517-8

Key clinical point: Zavegepant nasal spray was effective in the acute treatment of migraine, with favorable tolerability and safety profiles.

Major finding: At 2 hours post-dose, higher proportions of patients treated with zavegepant vs placebo were free from pain (risk difference 8.8 percentage points; P < .0001) and from their most bothersome symptom (risk difference 8.7 percentage points; P = .0012). Dysgeusia (21% vs 5%), nasal discomfort (4% vs 1%), and nausea (3% vs 1%) were the most common adverse events in the zavegepant vs placebo group.

Study details: Findings are from a phase 3 trial including 1405 patients with ≥1-year history of migraine with or without aura who were randomly assigned to receive zavegepant 10 mg nasal spray (n = 703) or matching placebo (n = 702).

Disclosures: This study was funded by Biohaven Pharmaceuticals. Some authors declared being employees of and holding stocks or stock options in Biohaven Pharmaceuticals. Some others declared ties with various sources, including Biohaven Pharmaceuticals.

Source: Lipton RB et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: A phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol. 2023;22(3):209-217 (Mar). Doi: 10.1016/S1474-4422(22)00517-8

Vaginal swabs are more effective than urine analysis in detecting certain types of sexually transmitted infections, researchers have found.

In the study, which was published online in the Annals of Family Medicine, investigators found that the diagnostic sensitivity of commercially available vaginal swabs was significantly greater than that of urine tests in detecting certain infections, including those caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

Researchers studied chlamydia and gonorrhea, which are two of the most frequently reported STIs in the United States. Trichomoniasis is the most curable nonviral STI globally, with 156 million cases worldwide in 2016.

The Centers for Disease Control and Prevention has long recommended that vaginal swabs be used to produce optimal samples.

But despite the CDC’s recommendation, urine analysis for these STIs is more commonly used than vaginal swabs among U.S. health care providers.

“We’re using a poor sample type, and we can do better,” said Barbara Van Der Pol, PhD, a professor of medicine and public health at the University of Alabama at Birmingham and an author of the new study, a meta-analysis of 97 studies published between 1995 and 2021.

Vaginal swabs for chlamydia trachomatis had a diagnostic sensitivity of 94.1% (95% confidence interval, 93.2%-94.9%; P < .001), higher than urine testing (86.9%; 95% CI, 85.6%-88.0%; P < .001). The pooled sensitivity estimates for Neisseria gonorrhoeae were 96.5% (95% CI, 94.8%-97.7%; P < .001) for vaginal swabs and 90.7% (95% CI, 88.4%-92.5%; P < .001) for urine specimens.

The difference in pooled sensitivity estimates between vaginal swabs and urine analyses for Trichomonas vaginalis was 98% (95% CI, 97.0%-98.7%; P < .001) for vaginal swabs and 95.1% (95% CI, 93.6%-96.3%) for urine specimens.

STIs included in the study are not typically found in the urethra and appear in urine analyses only if cervical or vaginal cells have dripped into a urine sample. Dr. Van Der Pol and her colleagues estimated that the use of urine samples rather than vaginal swabs may result in more than 400,000 undiagnosed infections annually.

Undiagnosed and untreated STIs can lead to transmissions of the infection as well as infertility and can have negative effects on romantic relationships, according to Dr. Van Der Pol.

Sarah Wood, MD, an attending physician at Children’s Hospital of Philadelphia, said some health care providers may use urine analysis because patients may be more comfortable with this method. The approach also can be more convenient for medical offices: All they must do is hand a specimen container to the patient.

Conversations between clinicians and patients about vaginal swabbing may be considered “sensitive” and the swabbing more invasive, Dr. Wood, an author of an editorial accompanying the journal article, said. Clinicians may also lack awareness that the swab is a more sensitive method of detecting these STIs.

“We all want to do what’s right for our patient, but we often don’t know what’s right for the patient,” Dr. Wood said. “I don’t think people are really aware of a potential real difference in outcomes with one method over the other.”

Dr. Wood advised making STI screening using vaginal swabs more common by “offering universal opt-out screening, so not waiting until you find out if someone’s having sex but just sort of saying, ‘Hey, across our practice, we screen everybody for chlamydia. Is that something that you want to do today?’ That approach sort of takes out the piece of talking about sex, talking about sexual activity.”

Dr. Van Der Pol, who said she has worked in STI diagnostics for 40 years, said she was not surprised by the results and hopes the study changes how samples are collected and used.

“I really hope that it influences practice so that we really start using vaginal swabs, because it gives us better diagnostics for chlamydia and gonorrhea,” Dr. Van Der Pol said.

“Also, then starting to think about comprehensive women’s care in such a way that they actually order other tests on that same sample if a woman is presenting with complaints.”

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

Vaginal swabs are more effective than urine analysis in detecting certain types of sexually transmitted infections, researchers have found.

In the study, which was published online in the Annals of Family Medicine, investigators found that the diagnostic sensitivity of commercially available vaginal swabs was significantly greater than that of urine tests in detecting certain infections, including those caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

Researchers studied chlamydia and gonorrhea, which are two of the most frequently reported STIs in the United States. Trichomoniasis is the most curable nonviral STI globally, with 156 million cases worldwide in 2016.

The Centers for Disease Control and Prevention has long recommended that vaginal swabs be used to produce optimal samples.

But despite the CDC’s recommendation, urine analysis for these STIs is more commonly used than vaginal swabs among U.S. health care providers.

“We’re using a poor sample type, and we can do better,” said Barbara Van Der Pol, PhD, a professor of medicine and public health at the University of Alabama at Birmingham and an author of the new study, a meta-analysis of 97 studies published between 1995 and 2021.

Vaginal swabs for chlamydia trachomatis had a diagnostic sensitivity of 94.1% (95% confidence interval, 93.2%-94.9%; P < .001), higher than urine testing (86.9%; 95% CI, 85.6%-88.0%; P < .001). The pooled sensitivity estimates for Neisseria gonorrhoeae were 96.5% (95% CI, 94.8%-97.7%; P < .001) for vaginal swabs and 90.7% (95% CI, 88.4%-92.5%; P < .001) for urine specimens.

The difference in pooled sensitivity estimates between vaginal swabs and urine analyses for Trichomonas vaginalis was 98% (95% CI, 97.0%-98.7%; P < .001) for vaginal swabs and 95.1% (95% CI, 93.6%-96.3%) for urine specimens.

STIs included in the study are not typically found in the urethra and appear in urine analyses only if cervical or vaginal cells have dripped into a urine sample. Dr. Van Der Pol and her colleagues estimated that the use of urine samples rather than vaginal swabs may result in more than 400,000 undiagnosed infections annually.

Undiagnosed and untreated STIs can lead to transmissions of the infection as well as infertility and can have negative effects on romantic relationships, according to Dr. Van Der Pol.

Sarah Wood, MD, an attending physician at Children’s Hospital of Philadelphia, said some health care providers may use urine analysis because patients may be more comfortable with this method. The approach also can be more convenient for medical offices: All they must do is hand a specimen container to the patient.

Conversations between clinicians and patients about vaginal swabbing may be considered “sensitive” and the swabbing more invasive, Dr. Wood, an author of an editorial accompanying the journal article, said. Clinicians may also lack awareness that the swab is a more sensitive method of detecting these STIs.

“We all want to do what’s right for our patient, but we often don’t know what’s right for the patient,” Dr. Wood said. “I don’t think people are really aware of a potential real difference in outcomes with one method over the other.”

Dr. Wood advised making STI screening using vaginal swabs more common by “offering universal opt-out screening, so not waiting until you find out if someone’s having sex but just sort of saying, ‘Hey, across our practice, we screen everybody for chlamydia. Is that something that you want to do today?’ That approach sort of takes out the piece of talking about sex, talking about sexual activity.”

Dr. Van Der Pol, who said she has worked in STI diagnostics for 40 years, said she was not surprised by the results and hopes the study changes how samples are collected and used.

“I really hope that it influences practice so that we really start using vaginal swabs, because it gives us better diagnostics for chlamydia and gonorrhea,” Dr. Van Der Pol said.

“Also, then starting to think about comprehensive women’s care in such a way that they actually order other tests on that same sample if a woman is presenting with complaints.”

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

Vaginal swabs are more effective than urine analysis in detecting certain types of sexually transmitted infections, researchers have found.

In the study, which was published online in the Annals of Family Medicine, investigators found that the diagnostic sensitivity of commercially available vaginal swabs was significantly greater than that of urine tests in detecting certain infections, including those caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

Researchers studied chlamydia and gonorrhea, which are two of the most frequently reported STIs in the United States. Trichomoniasis is the most curable nonviral STI globally, with 156 million cases worldwide in 2016.

The Centers for Disease Control and Prevention has long recommended that vaginal swabs be used to produce optimal samples.

But despite the CDC’s recommendation, urine analysis for these STIs is more commonly used than vaginal swabs among U.S. health care providers.

“We’re using a poor sample type, and we can do better,” said Barbara Van Der Pol, PhD, a professor of medicine and public health at the University of Alabama at Birmingham and an author of the new study, a meta-analysis of 97 studies published between 1995 and 2021.

Vaginal swabs for chlamydia trachomatis had a diagnostic sensitivity of 94.1% (95% confidence interval, 93.2%-94.9%; P < .001), higher than urine testing (86.9%; 95% CI, 85.6%-88.0%; P < .001). The pooled sensitivity estimates for Neisseria gonorrhoeae were 96.5% (95% CI, 94.8%-97.7%; P < .001) for vaginal swabs and 90.7% (95% CI, 88.4%-92.5%; P < .001) for urine specimens.

The difference in pooled sensitivity estimates between vaginal swabs and urine analyses for Trichomonas vaginalis was 98% (95% CI, 97.0%-98.7%; P < .001) for vaginal swabs and 95.1% (95% CI, 93.6%-96.3%) for urine specimens.

STIs included in the study are not typically found in the urethra and appear in urine analyses only if cervical or vaginal cells have dripped into a urine sample. Dr. Van Der Pol and her colleagues estimated that the use of urine samples rather than vaginal swabs may result in more than 400,000 undiagnosed infections annually.

Undiagnosed and untreated STIs can lead to transmissions of the infection as well as infertility and can have negative effects on romantic relationships, according to Dr. Van Der Pol.

Sarah Wood, MD, an attending physician at Children’s Hospital of Philadelphia, said some health care providers may use urine analysis because patients may be more comfortable with this method. The approach also can be more convenient for medical offices: All they must do is hand a specimen container to the patient.

Conversations between clinicians and patients about vaginal swabbing may be considered “sensitive” and the swabbing more invasive, Dr. Wood, an author of an editorial accompanying the journal article, said. Clinicians may also lack awareness that the swab is a more sensitive method of detecting these STIs.

“We all want to do what’s right for our patient, but we often don’t know what’s right for the patient,” Dr. Wood said. “I don’t think people are really aware of a potential real difference in outcomes with one method over the other.”

Dr. Wood advised making STI screening using vaginal swabs more common by “offering universal opt-out screening, so not waiting until you find out if someone’s having sex but just sort of saying, ‘Hey, across our practice, we screen everybody for chlamydia. Is that something that you want to do today?’ That approach sort of takes out the piece of talking about sex, talking about sexual activity.”

Dr. Van Der Pol, who said she has worked in STI diagnostics for 40 years, said she was not surprised by the results and hopes the study changes how samples are collected and used.

“I really hope that it influences practice so that we really start using vaginal swabs, because it gives us better diagnostics for chlamydia and gonorrhea,” Dr. Van Der Pol said.

“Also, then starting to think about comprehensive women’s care in such a way that they actually order other tests on that same sample if a woman is presenting with complaints.”

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

The Drug Enforcement Administration is warning the public about a sharp increase in trafficking in fentanyl mixed with the animal tranquilizer xylazine, stating that the agency has seized mixtures of the two drugs in 48 states.

The DEA warning comes on the heels of a Food and Drug Administration announcement that it would begin more closely monitoring imports of the raw materials and bulk shipments of xylazine, also known as “tranq” and “zombie drug.”

Xylazine was first approved by the FDA in 1972 as a sedative and analgesic for use only in animals, but is increasingly being detected in illicit street drugs, and is often mixed with fentanyl, cocaine, and methamphetamine.

The FDA warned in November that naloxone (Narcan) would not reverse xylazine-related overdoses because the tranquilizer is not an opioid. It does suppress respiration and repeated exposures may lead to dependence and withdrawal, said the agency. Users are also experiencing severe necrosis at injection sites.

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA Administrator Anne Milgram in a statement. “The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

Xylazine use has spread quickly, from its start in the Philadelphia area to the Northeast, the South, and most recently the West.

Citing data from the Centers for Disease Control and Prevention, the DEA said that 66% of the 107,735 overdose deaths for the year ending August 2022 involved synthetic opioids such as fentanyl. The DEA said that the Sinaloa Cartel and Jalisco Cartel in Mexico, using chemicals sourced from China, are primarily responsible for trafficking fentanyl in the United States.

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

The Drug Enforcement Administration is warning the public about a sharp increase in trafficking in fentanyl mixed with the animal tranquilizer xylazine, stating that the agency has seized mixtures of the two drugs in 48 states.

The DEA warning comes on the heels of a Food and Drug Administration announcement that it would begin more closely monitoring imports of the raw materials and bulk shipments of xylazine, also known as “tranq” and “zombie drug.”

Xylazine was first approved by the FDA in 1972 as a sedative and analgesic for use only in animals, but is increasingly being detected in illicit street drugs, and is often mixed with fentanyl, cocaine, and methamphetamine.

The FDA warned in November that naloxone (Narcan) would not reverse xylazine-related overdoses because the tranquilizer is not an opioid. It does suppress respiration and repeated exposures may lead to dependence and withdrawal, said the agency. Users are also experiencing severe necrosis at injection sites.

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA Administrator Anne Milgram in a statement. “The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

Xylazine use has spread quickly, from its start in the Philadelphia area to the Northeast, the South, and most recently the West.

Citing data from the Centers for Disease Control and Prevention, the DEA said that 66% of the 107,735 overdose deaths for the year ending August 2022 involved synthetic opioids such as fentanyl. The DEA said that the Sinaloa Cartel and Jalisco Cartel in Mexico, using chemicals sourced from China, are primarily responsible for trafficking fentanyl in the United States.

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

The Drug Enforcement Administration is warning the public about a sharp increase in trafficking in fentanyl mixed with the animal tranquilizer xylazine, stating that the agency has seized mixtures of the two drugs in 48 states.

The DEA warning comes on the heels of a Food and Drug Administration announcement that it would begin more closely monitoring imports of the raw materials and bulk shipments of xylazine, also known as “tranq” and “zombie drug.”

Xylazine was first approved by the FDA in 1972 as a sedative and analgesic for use only in animals, but is increasingly being detected in illicit street drugs, and is often mixed with fentanyl, cocaine, and methamphetamine.

The FDA warned in November that naloxone (Narcan) would not reverse xylazine-related overdoses because the tranquilizer is not an opioid. It does suppress respiration and repeated exposures may lead to dependence and withdrawal, said the agency. Users are also experiencing severe necrosis at injection sites.

“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said DEA Administrator Anne Milgram in a statement. “The DEA Laboratory System is reporting that in 2022 approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”

Xylazine use has spread quickly, from its start in the Philadelphia area to the Northeast, the South, and most recently the West.

Citing data from the Centers for Disease Control and Prevention, the DEA said that 66% of the 107,735 overdose deaths for the year ending August 2022 involved synthetic opioids such as fentanyl. The DEA said that the Sinaloa Cartel and Jalisco Cartel in Mexico, using chemicals sourced from China, are primarily responsible for trafficking fentanyl in the United States.

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

At a joint meeting of two Food and Drug Administration advisory committees on March 29, panelists voted to modify two aspects of the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, a drug for severe, nodular acne that is highly teratogenic.

The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.

Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.

Listed options and the number of votes for each were:

• Only with the first prescription as part of patient enrollment (10)
• Monthly (1)
• Every 120 days (6)
• Some other frequency (5)

For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.

Lack of data

On both questions, several advisory committee members cited a lack of data on which they could base their decision.

On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.

“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”

The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.

The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.

They were also tasked with discussing other REMS requirements without taking a vote on each topic.

Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.

The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

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

At a joint meeting of two Food and Drug Administration advisory committees on March 29, panelists voted to modify two aspects of the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, a drug for severe, nodular acne that is highly teratogenic.

The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.

Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.

Listed options and the number of votes for each were:

• Only with the first prescription as part of patient enrollment (10)
• Monthly (1)
• Every 120 days (6)
• Some other frequency (5)

For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.

Lack of data

On both questions, several advisory committee members cited a lack of data on which they could base their decision.

On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.

“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”

The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.

The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.

They were also tasked with discussing other REMS requirements without taking a vote on each topic.

Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.

The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

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

At a joint meeting of two Food and Drug Administration advisory committees on March 29, panelists voted to modify two aspects of the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, a drug for severe, nodular acne that is highly teratogenic.

The first vote was on whether to continue the 19-day lockout period for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the 7-day prescription window. Those patients currently have to wait 19 days to get their second pregnancy test and receive the medication.

Most (17) of the 22 voting members voted not to continue the 19-day period; 4 voted to keep it; and 1 abstained. But there was no consensus on when the second pregnancy test should occur if the 19-day lockout is changed.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among those voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

The second question concerned patients who cannot become pregnant, and it asked when REMS should require that the prescriber document counseling the patient in the iPLEDGE system. The current requirement is monthly.

Listed options and the number of votes for each were:

• Only with the first prescription as part of patient enrollment (10)
• Monthly (1)
• Every 120 days (6)
• Some other frequency (5)

For this question too, while the members largely agreed the current monthly requirement is too burdensome, there was little agreement on what the most appropriate interval should be.

Lack of data

On both questions, several advisory committee members cited a lack of data on which they could base their decision.

On the documentation question, Megha Tollefson, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., said she voted for the fourth option (some other frequency) with the thought of yearly attestation.

“As a part of this, providers have to provide monthly counseling,” Dr. Tollefson said. “This is just a documentation requirement in the iPLEDGE system. I think most prescribers do document their monthly counseling in their own medical records. I would say it would be okay not to redocument that in iPLEDGE.”

The two votes came at the end of the second day of a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee in which experts addressed ways to improve the iPLEDGE REMS for isotretinoin. A transition to a new platform for the iPLEDGE program caused chaos after its rollout at the end of 2021, resulting in extensive delays and denial of prescriptions.

The committees sought to balance reducing burden with maintaining safety and preventing fetal exposures to isotretinoin.

They were also tasked with discussing other REMS requirements without taking a vote on each topic.

Among those topics was whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most who spoke to the issue agreed that home tests should continue in an effort to increase access and decrease burden. Members suggested safeguards against falsified results that have been documented, including assigning names and barcodes to the test results and uploading the verification to the iPLEDGE website.

The advisory committees also discussed recommendations to encourage more participation in the iPLEDGE Pregnancy Registry.

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

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

Getting sweet on sweat

Are you the sort of person who struggles in social situations? Have the past 3 years been a secret respite from the terror and exhaustion of meeting new people? We understand your plight. People kind of suck. And you don’t have to look far to be reminded of it.

Unfortunately, on occasion we all have to interact with other human beings. If you suffer from social anxiety, this is not a fun thing to do. But new research indicates that there may be a way to alleviate the stress for those with social anxiety: armpits.

alex bracken/Unsplash

Specifically, sweat from the armpits of other people. Yes, this means a group of scientists gathered up some volunteers and collected their armpit sweat while the volunteers watched a variety of movies (horror, comedy, romance, etc.). Our condolences to the poor unpaid interns tasked with gathering the sweat.

Once they had their precious new medicine, the researchers took a group of women and administered a round of mindfulness therapy. Some of the participants then received the various sweats, while the rest were forced to smell only clean air. (The horror!) Lo and behold, the sweat groups had their anxiety scores reduced by about 40% after their therapy, compared with just 17% in the control group.

The researchers also found that the source of the sweat didn’t matter. Their study subjects responded the same to sweat excreted during a scary movie as they did to sweat from a comedy, a result that surprised the researchers. They suggested chemosignals in the sweat may affect the treatment response and advised further research. Which means more sweat collection! They plan on testing emotionally neutral movies next time, and if we can make a humble suggestion, they also should try the sweatiest movies.

Before the Food and Drug Administration can approve armpit sweat as a treatment for social anxiety, we have some advice for those shut-in introverts out there. Next time you have to interact with rabid extroverts, instead of shaking their hands, walk up to them and take a deep whiff of their armpits. Establish dominance. Someone will feel awkward, and science has proved it won’t be you.
 

The puff that vaccinates

Ever been shot with a Nerf gun or hit with a foam pool tube? More annoying than painful, right? If we asked if you’d rather get pelted with one of those than receive a traditional vaccine injection, you would choose the former. Maybe someday you actually will.

Dr. Jeremiah Gassensmith

During the boredom of the early pandemic lockdown, Jeremiah Gassensmith, PhD, of the department of chemistry and biochemistry at the University of Texas, Dallas, ordered a compressed gas–powered jet injection system to fool around with at home. Hey, who didn’t? Anyway, when it was time to go back to the lab he handed it over to one of his grad students, Yalini Wijesundara, and asked her to see what could be done with it.

In her tinkering she found that the jet injector could deliver metal-organic frameworks (MOFs) that can hold a bunch of different materials, like proteins and nucleic acids, through the skin.

Thus the “MOF-Jet” was born!

Jet injectors are nothing new, but they hurt. The MOF-Jet, however, is practically painless and cheaper than the gene guns that veterinarians use to inject biological cargo attached to the surface of a metal microparticle.

Changing the carrier gas also changes the time needed to break down the MOF and thus alters delivery of the drug inside. “If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take 4 or 5 days,” Ms. Wijesundara explained in a written statement. That means the same drug could be released over different timescales without changing its formulation.

While testing on onion cells and mice, Ms. Wijesundara noted that it was as easy as “pointing and shooting” to distribute the puff of gas into the cells. A saving grace to those with needle anxiety. Not that we would know anything about needle anxiety.

More testing needs to be done before bringing this technology to human use, obviously, but we’re looking forward to saying goodbye to that dreaded prick and hello to a puff.
 

Your hippocampus is showing

Brain anatomy is one of the many, many things that’s not really our thing, but we do know a cool picture when we see one. Case in point: The image just below, which happens to be a full-scale, single-cell resolution model of the CA1 region of the hippocampus that “replicates the structure and architecture of the area, along with the position and relative connectivity of the neurons,” according to a statement from the Human Brain Project.

Dr. Michele Migliore

“We have performed a data mining operation on high resolution images of the human hippocampus, obtained from the BigBrain database. The position of individual neurons has been derived from a detailed analysis of these images,” said senior author Michele Migliore, PhD, of the Italian National Research Council’s Institute of Biophysics in Palermo.

Yes, he did say BigBrain database. BigBrain is – we checked and it’s definitely not this – a 3D model of a brain that was sectioned into 7,404 slices just 20 micrometers thick and then scanned by MRI. Digital reconstruction of those slices was done by supercomputer and the results are now available for analysis.

Dr. Migliore and his associates developed an image-processing algorithm to obtain neuronal positioning distribution and an algorithm to generate neuronal connectivity by approximating the shapes of dendrites and axons. (Our brains are starting to hurt just trying to write this.) “Some fit into narrow cones, others have a broad complex extension that can be approximated by dedicated geometrical volumes, and the connectivity to nearby neurons changes accordingly,” explained lead author Daniela Gandolfi of the University of Modena (Italy) and Reggio Emilia.

The investigators have made their dataset and the extraction methodology available on the EBRAINS platform and through the Human Brain Project and are moving on to other brain regions. And then, once everyone can find their way in and around the old gray matter, it should bring an end to conversations like this, which no doubt occur between male and female neuroscientists every day:

“Arnold, I think we’re lost.”

“Don’t worry, Bev, I know where I’m going.”

“Stop and ask this lady for directions.”

“I said I can find it.”

“Just ask her.”

“Fine. Excuse me, ma’am, can you tell us how to get to the corpora quadrigemina from here?

Getting sweet on sweat

Are you the sort of person who struggles in social situations? Have the past 3 years been a secret respite from the terror and exhaustion of meeting new people? We understand your plight. People kind of suck. And you don’t have to look far to be reminded of it.

Unfortunately, on occasion we all have to interact with other human beings. If you suffer from social anxiety, this is not a fun thing to do. But new research indicates that there may be a way to alleviate the stress for those with social anxiety: armpits.

alex bracken/Unsplash

Specifically, sweat from the armpits of other people. Yes, this means a group of scientists gathered up some volunteers and collected their armpit sweat while the volunteers watched a variety of movies (horror, comedy, romance, etc.). Our condolences to the poor unpaid interns tasked with gathering the sweat.

Once they had their precious new medicine, the researchers took a group of women and administered a round of mindfulness therapy. Some of the participants then received the various sweats, while the rest were forced to smell only clean air. (The horror!) Lo and behold, the sweat groups had their anxiety scores reduced by about 40% after their therapy, compared with just 17% in the control group.

The researchers also found that the source of the sweat didn’t matter. Their study subjects responded the same to sweat excreted during a scary movie as they did to sweat from a comedy, a result that surprised the researchers. They suggested chemosignals in the sweat may affect the treatment response and advised further research. Which means more sweat collection! They plan on testing emotionally neutral movies next time, and if we can make a humble suggestion, they also should try the sweatiest movies.

Before the Food and Drug Administration can approve armpit sweat as a treatment for social anxiety, we have some advice for those shut-in introverts out there. Next time you have to interact with rabid extroverts, instead of shaking their hands, walk up to them and take a deep whiff of their armpits. Establish dominance. Someone will feel awkward, and science has proved it won’t be you.
 

The puff that vaccinates

Ever been shot with a Nerf gun or hit with a foam pool tube? More annoying than painful, right? If we asked if you’d rather get pelted with one of those than receive a traditional vaccine injection, you would choose the former. Maybe someday you actually will.

Dr. Jeremiah Gassensmith

During the boredom of the early pandemic lockdown, Jeremiah Gassensmith, PhD, of the department of chemistry and biochemistry at the University of Texas, Dallas, ordered a compressed gas–powered jet injection system to fool around with at home. Hey, who didn’t? Anyway, when it was time to go back to the lab he handed it over to one of his grad students, Yalini Wijesundara, and asked her to see what could be done with it.

In her tinkering she found that the jet injector could deliver metal-organic frameworks (MOFs) that can hold a bunch of different materials, like proteins and nucleic acids, through the skin.

Thus the “MOF-Jet” was born!

Jet injectors are nothing new, but they hurt. The MOF-Jet, however, is practically painless and cheaper than the gene guns that veterinarians use to inject biological cargo attached to the surface of a metal microparticle.

Changing the carrier gas also changes the time needed to break down the MOF and thus alters delivery of the drug inside. “If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take 4 or 5 days,” Ms. Wijesundara explained in a written statement. That means the same drug could be released over different timescales without changing its formulation.

While testing on onion cells and mice, Ms. Wijesundara noted that it was as easy as “pointing and shooting” to distribute the puff of gas into the cells. A saving grace to those with needle anxiety. Not that we would know anything about needle anxiety.

More testing needs to be done before bringing this technology to human use, obviously, but we’re looking forward to saying goodbye to that dreaded prick and hello to a puff.
 

Your hippocampus is showing

Brain anatomy is one of the many, many things that’s not really our thing, but we do know a cool picture when we see one. Case in point: The image just below, which happens to be a full-scale, single-cell resolution model of the CA1 region of the hippocampus that “replicates the structure and architecture of the area, along with the position and relative connectivity of the neurons,” according to a statement from the Human Brain Project.

Dr. Michele Migliore

“We have performed a data mining operation on high resolution images of the human hippocampus, obtained from the BigBrain database. The position of individual neurons has been derived from a detailed analysis of these images,” said senior author Michele Migliore, PhD, of the Italian National Research Council’s Institute of Biophysics in Palermo.

Yes, he did say BigBrain database. BigBrain is – we checked and it’s definitely not this – a 3D model of a brain that was sectioned into 7,404 slices just 20 micrometers thick and then scanned by MRI. Digital reconstruction of those slices was done by supercomputer and the results are now available for analysis.

Dr. Migliore and his associates developed an image-processing algorithm to obtain neuronal positioning distribution and an algorithm to generate neuronal connectivity by approximating the shapes of dendrites and axons. (Our brains are starting to hurt just trying to write this.) “Some fit into narrow cones, others have a broad complex extension that can be approximated by dedicated geometrical volumes, and the connectivity to nearby neurons changes accordingly,” explained lead author Daniela Gandolfi of the University of Modena (Italy) and Reggio Emilia.

The investigators have made their dataset and the extraction methodology available on the EBRAINS platform and through the Human Brain Project and are moving on to other brain regions. And then, once everyone can find their way in and around the old gray matter, it should bring an end to conversations like this, which no doubt occur between male and female neuroscientists every day:

“Arnold, I think we’re lost.”

“Don’t worry, Bev, I know where I’m going.”

“Stop and ask this lady for directions.”

“I said I can find it.”

“Just ask her.”

“Fine. Excuse me, ma’am, can you tell us how to get to the corpora quadrigemina from here?

Getting sweet on sweat

Are you the sort of person who struggles in social situations? Have the past 3 years been a secret respite from the terror and exhaustion of meeting new people? We understand your plight. People kind of suck. And you don’t have to look far to be reminded of it.

Unfortunately, on occasion we all have to interact with other human beings. If you suffer from social anxiety, this is not a fun thing to do. But new research indicates that there may be a way to alleviate the stress for those with social anxiety: armpits.

alex bracken/Unsplash

Specifically, sweat from the armpits of other people. Yes, this means a group of scientists gathered up some volunteers and collected their armpit sweat while the volunteers watched a variety of movies (horror, comedy, romance, etc.). Our condolences to the poor unpaid interns tasked with gathering the sweat.

Once they had their precious new medicine, the researchers took a group of women and administered a round of mindfulness therapy. Some of the participants then received the various sweats, while the rest were forced to smell only clean air. (The horror!) Lo and behold, the sweat groups had their anxiety scores reduced by about 40% after their therapy, compared with just 17% in the control group.

The researchers also found that the source of the sweat didn’t matter. Their study subjects responded the same to sweat excreted during a scary movie as they did to sweat from a comedy, a result that surprised the researchers. They suggested chemosignals in the sweat may affect the treatment response and advised further research. Which means more sweat collection! They plan on testing emotionally neutral movies next time, and if we can make a humble suggestion, they also should try the sweatiest movies.

Before the Food and Drug Administration can approve armpit sweat as a treatment for social anxiety, we have some advice for those shut-in introverts out there. Next time you have to interact with rabid extroverts, instead of shaking their hands, walk up to them and take a deep whiff of their armpits. Establish dominance. Someone will feel awkward, and science has proved it won’t be you.
 

The puff that vaccinates

Ever been shot with a Nerf gun or hit with a foam pool tube? More annoying than painful, right? If we asked if you’d rather get pelted with one of those than receive a traditional vaccine injection, you would choose the former. Maybe someday you actually will.

Dr. Jeremiah Gassensmith

During the boredom of the early pandemic lockdown, Jeremiah Gassensmith, PhD, of the department of chemistry and biochemistry at the University of Texas, Dallas, ordered a compressed gas–powered jet injection system to fool around with at home. Hey, who didn’t? Anyway, when it was time to go back to the lab he handed it over to one of his grad students, Yalini Wijesundara, and asked her to see what could be done with it.

In her tinkering she found that the jet injector could deliver metal-organic frameworks (MOFs) that can hold a bunch of different materials, like proteins and nucleic acids, through the skin.

Thus the “MOF-Jet” was born!

Jet injectors are nothing new, but they hurt. The MOF-Jet, however, is practically painless and cheaper than the gene guns that veterinarians use to inject biological cargo attached to the surface of a metal microparticle.

Changing the carrier gas also changes the time needed to break down the MOF and thus alters delivery of the drug inside. “If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take 4 or 5 days,” Ms. Wijesundara explained in a written statement. That means the same drug could be released over different timescales without changing its formulation.

While testing on onion cells and mice, Ms. Wijesundara noted that it was as easy as “pointing and shooting” to distribute the puff of gas into the cells. A saving grace to those with needle anxiety. Not that we would know anything about needle anxiety.

More testing needs to be done before bringing this technology to human use, obviously, but we’re looking forward to saying goodbye to that dreaded prick and hello to a puff.
 

Your hippocampus is showing

Brain anatomy is one of the many, many things that’s not really our thing, but we do know a cool picture when we see one. Case in point: The image just below, which happens to be a full-scale, single-cell resolution model of the CA1 region of the hippocampus that “replicates the structure and architecture of the area, along with the position and relative connectivity of the neurons,” according to a statement from the Human Brain Project.

Dr. Michele Migliore

“We have performed a data mining operation on high resolution images of the human hippocampus, obtained from the BigBrain database. The position of individual neurons has been derived from a detailed analysis of these images,” said senior author Michele Migliore, PhD, of the Italian National Research Council’s Institute of Biophysics in Palermo.

Yes, he did say BigBrain database. BigBrain is – we checked and it’s definitely not this – a 3D model of a brain that was sectioned into 7,404 slices just 20 micrometers thick and then scanned by MRI. Digital reconstruction of those slices was done by supercomputer and the results are now available for analysis.

Dr. Migliore and his associates developed an image-processing algorithm to obtain neuronal positioning distribution and an algorithm to generate neuronal connectivity by approximating the shapes of dendrites and axons. (Our brains are starting to hurt just trying to write this.) “Some fit into narrow cones, others have a broad complex extension that can be approximated by dedicated geometrical volumes, and the connectivity to nearby neurons changes accordingly,” explained lead author Daniela Gandolfi of the University of Modena (Italy) and Reggio Emilia.

The investigators have made their dataset and the extraction methodology available on the EBRAINS platform and through the Human Brain Project and are moving on to other brain regions. And then, once everyone can find their way in and around the old gray matter, it should bring an end to conversations like this, which no doubt occur between male and female neuroscientists every day:

“Arnold, I think we’re lost.”

“Don’t worry, Bev, I know where I’m going.”

“Stop and ask this lady for directions.”

“I said I can find it.”

“Just ask her.”

“Fine. Excuse me, ma’am, can you tell us how to get to the corpora quadrigemina from here?

In a real-life clinic setting study aimed at determining phenotypic associations of mucus plugging in moderate to severe asthma patients, those with mucus plugging had worse lung function, more frequent severe exacerbations needing oral corticosteroids, and higher T2 biomarkers.

Rory Chan, MBChB, of the University of Dundee (Scotland) and colleagues found conversely that the presence of these features was associated with an increased likelihood of mucus plugging.

Important pathophysiological characteristics of persistent asthma include mucus plugging, goblet cell hyperplasia, smooth muscle hypertrophy, and eosinophilic infiltration. Mucus plugging contributes significantly to airway obstruction and death in acute asthma, the investigators stated, noting further that the understanding of mucus plugging’s role in chronic asthma is increasing.

Their retrospective cohort study included 126 patients with respiratory physician-diagnosed moderate to severe asthma who had attended their clinic (January 2016–March 2022) and were receiving daily doses of inhaled corticosteroid (ICS) (≥ 800 mcg) and a second-line controller. All had prior high-resolution CT (HRCT) scans with mucus plugs identified by an experienced thoracic radiologist. Prior to the start of biologic therapy, a mucus plug score (MPS) signifying the number of affected lung segments (0-20) was calculated subsequently and considered along with pulmonary function testing, T2 inflammatory markers, asthma control data, and measures of peripheral blood eosinophils (PBE), as well as total IgG and IgE antibodies to Apergillus fumigatus.

The analysis showed that reduced forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio (OR, 3.01; 95% confidence interval, 1.14-7.97), two or more exacerbations per year (OR, 5.00; 95% CI, 1.55-16.11), raised PBE (OR, 3.23; 95% CI, 1.16-8.96), raised total IgE (OR, 3.20; 95% CI, 1.09-9.37), and Aspergillus fumigatus IgE titers (OR, 9.37; 95% CI, 1.82-48.20) all conferred significantly higher likelihood of the presence of mucus plugging. Highest prevalence of mucus plugs was in the right and left lower lung lobes (about 26% vs. about 10% and 14% in the middle and upper lobes).

Adjusted ORs in patients with impaired FEV₁/FVC, showed the likelihood of mucus plugging to be 67% higher. In those with frequent exacerbations, they were 80% higher, and in those with raised PBE and IgE, 69% higher. Patients without mucus plugging had preserved FEV₁ and FEV₁/FVC.

Asthma patients with mucus plugging in the study exhibited higher levels of routinely measured T2 biomarkers, including blood eosinophils, FeNO, and total IgE, with median values all exceeding traditionally accepted cut points. Although patients with mucus plugging were receiving significantly higher ICS doses, and despite the suppressive effect of ICS on FeNO, they still had higher FeNO levels. “We therefore postulate that asthma patients with the MP phenotype might potentially experience greater treatment response to biologics targeting the underlying inflammatory endotype,” the investigators stated, adding that “the presence of mucus plugging should be recognized as a treatable trait for patients with severe asthma in terms of targeting therapy with biologics.”

They wrote that, “in a real-life clinic setting, the presence of mucus plugging detected on HRCT was associated with more severe exacerbations, more severe airflow obstruction, and greater T2 inflammation. This, in turn, suggests that imaging should be part of the routine workup of patients with poorly controlled severe asthma.”

In an accompanying editorial, Jorge Cedano, MD, Jiwoong Choi, PhD, and Mario Castro, MD, MPH, of the University of Kansas, Kansas City, cited that the prevalence and contribution of mucus plugging in the pathophysiology and morbidity of uncontrolled asthma is much greater than has been appreciated. They focused particularly on the suggestion that, even after adjusting for confounders, molds such as Apergillus may play a causal role, along with blood eosinophils, fractional exhaled nitric oxide, and total IgE, in T2 inflammation.

While current biologic therapies targeting the T2 phenotype have not yet been shown to reverse the progressive loss of lung function or lung remodeling process, the editorialists referenced a recent post hoc analysis of the CASCADE study showing mucus plugging reduction with the biologic tezepelumab versus placebo correlated with lung function improvement. “At least 20% of patients with moderate to severe asthma will experience progressive decline in lung function, more exacerbations, and worse asthma control despite the use of controller therapies. If physicians could identify the MP phenotype using computed tomography, then potentially earlier treatment with biologic therapy may improve asthma control and prevent future decline in lung function,” they said.

The study limitations listed included its retrospective observational nature and the fact that the study had only one senior thoracic radiologist interpreting the lung scans.

The study authors cited numerous conflicts of interest with pharmaceutical companies and medical societies. Dr. Castro reported affiliation or involvement in multiple organizations or entities with a financial or nonfinancial interest in the subject matter or materials discussed in the article.

In a real-life clinic setting study aimed at determining phenotypic associations of mucus plugging in moderate to severe asthma patients, those with mucus plugging had worse lung function, more frequent severe exacerbations needing oral corticosteroids, and higher T2 biomarkers.

Rory Chan, MBChB, of the University of Dundee (Scotland) and colleagues found conversely that the presence of these features was associated with an increased likelihood of mucus plugging.

Important pathophysiological characteristics of persistent asthma include mucus plugging, goblet cell hyperplasia, smooth muscle hypertrophy, and eosinophilic infiltration. Mucus plugging contributes significantly to airway obstruction and death in acute asthma, the investigators stated, noting further that the understanding of mucus plugging’s role in chronic asthma is increasing.

Their retrospective cohort study included 126 patients with respiratory physician-diagnosed moderate to severe asthma who had attended their clinic (January 2016–March 2022) and were receiving daily doses of inhaled corticosteroid (ICS) (≥ 800 mcg) and a second-line controller. All had prior high-resolution CT (HRCT) scans with mucus plugs identified by an experienced thoracic radiologist. Prior to the start of biologic therapy, a mucus plug score (MPS) signifying the number of affected lung segments (0-20) was calculated subsequently and considered along with pulmonary function testing, T2 inflammatory markers, asthma control data, and measures of peripheral blood eosinophils (PBE), as well as total IgG and IgE antibodies to Apergillus fumigatus.

The analysis showed that reduced forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio (OR, 3.01; 95% confidence interval, 1.14-7.97), two or more exacerbations per year (OR, 5.00; 95% CI, 1.55-16.11), raised PBE (OR, 3.23; 95% CI, 1.16-8.96), raised total IgE (OR, 3.20; 95% CI, 1.09-9.37), and Aspergillus fumigatus IgE titers (OR, 9.37; 95% CI, 1.82-48.20) all conferred significantly higher likelihood of the presence of mucus plugging. Highest prevalence of mucus plugs was in the right and left lower lung lobes (about 26% vs. about 10% and 14% in the middle and upper lobes).

Adjusted ORs in patients with impaired FEV₁/FVC, showed the likelihood of mucus plugging to be 67% higher. In those with frequent exacerbations, they were 80% higher, and in those with raised PBE and IgE, 69% higher. Patients without mucus plugging had preserved FEV₁ and FEV₁/FVC.

Asthma patients with mucus plugging in the study exhibited higher levels of routinely measured T2 biomarkers, including blood eosinophils, FeNO, and total IgE, with median values all exceeding traditionally accepted cut points. Although patients with mucus plugging were receiving significantly higher ICS doses, and despite the suppressive effect of ICS on FeNO, they still had higher FeNO levels. “We therefore postulate that asthma patients with the MP phenotype might potentially experience greater treatment response to biologics targeting the underlying inflammatory endotype,” the investigators stated, adding that “the presence of mucus plugging should be recognized as a treatable trait for patients with severe asthma in terms of targeting therapy with biologics.”

They wrote that, “in a real-life clinic setting, the presence of mucus plugging detected on HRCT was associated with more severe exacerbations, more severe airflow obstruction, and greater T2 inflammation. This, in turn, suggests that imaging should be part of the routine workup of patients with poorly controlled severe asthma.”

In an accompanying editorial, Jorge Cedano, MD, Jiwoong Choi, PhD, and Mario Castro, MD, MPH, of the University of Kansas, Kansas City, cited that the prevalence and contribution of mucus plugging in the pathophysiology and morbidity of uncontrolled asthma is much greater than has been appreciated. They focused particularly on the suggestion that, even after adjusting for confounders, molds such as Apergillus may play a causal role, along with blood eosinophils, fractional exhaled nitric oxide, and total IgE, in T2 inflammation.

While current biologic therapies targeting the T2 phenotype have not yet been shown to reverse the progressive loss of lung function or lung remodeling process, the editorialists referenced a recent post hoc analysis of the CASCADE study showing mucus plugging reduction with the biologic tezepelumab versus placebo correlated with lung function improvement. “At least 20% of patients with moderate to severe asthma will experience progressive decline in lung function, more exacerbations, and worse asthma control despite the use of controller therapies. If physicians could identify the MP phenotype using computed tomography, then potentially earlier treatment with biologic therapy may improve asthma control and prevent future decline in lung function,” they said.

The study limitations listed included its retrospective observational nature and the fact that the study had only one senior thoracic radiologist interpreting the lung scans.

The study authors cited numerous conflicts of interest with pharmaceutical companies and medical societies. Dr. Castro reported affiliation or involvement in multiple organizations or entities with a financial or nonfinancial interest in the subject matter or materials discussed in the article.

In a real-life clinic setting study aimed at determining phenotypic associations of mucus plugging in moderate to severe asthma patients, those with mucus plugging had worse lung function, more frequent severe exacerbations needing oral corticosteroids, and higher T2 biomarkers.

Rory Chan, MBChB, of the University of Dundee (Scotland) and colleagues found conversely that the presence of these features was associated with an increased likelihood of mucus plugging.

Important pathophysiological characteristics of persistent asthma include mucus plugging, goblet cell hyperplasia, smooth muscle hypertrophy, and eosinophilic infiltration. Mucus plugging contributes significantly to airway obstruction and death in acute asthma, the investigators stated, noting further that the understanding of mucus plugging’s role in chronic asthma is increasing.

Their retrospective cohort study included 126 patients with respiratory physician-diagnosed moderate to severe asthma who had attended their clinic (January 2016–March 2022) and were receiving daily doses of inhaled corticosteroid (ICS) (≥ 800 mcg) and a second-line controller. All had prior high-resolution CT (HRCT) scans with mucus plugs identified by an experienced thoracic radiologist. Prior to the start of biologic therapy, a mucus plug score (MPS) signifying the number of affected lung segments (0-20) was calculated subsequently and considered along with pulmonary function testing, T2 inflammatory markers, asthma control data, and measures of peripheral blood eosinophils (PBE), as well as total IgG and IgE antibodies to Apergillus fumigatus.

The analysis showed that reduced forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio (OR, 3.01; 95% confidence interval, 1.14-7.97), two or more exacerbations per year (OR, 5.00; 95% CI, 1.55-16.11), raised PBE (OR, 3.23; 95% CI, 1.16-8.96), raised total IgE (OR, 3.20; 95% CI, 1.09-9.37), and Aspergillus fumigatus IgE titers (OR, 9.37; 95% CI, 1.82-48.20) all conferred significantly higher likelihood of the presence of mucus plugging. Highest prevalence of mucus plugs was in the right and left lower lung lobes (about 26% vs. about 10% and 14% in the middle and upper lobes).

Adjusted ORs in patients with impaired FEV₁/FVC, showed the likelihood of mucus plugging to be 67% higher. In those with frequent exacerbations, they were 80% higher, and in those with raised PBE and IgE, 69% higher. Patients without mucus plugging had preserved FEV₁ and FEV₁/FVC.

Asthma patients with mucus plugging in the study exhibited higher levels of routinely measured T2 biomarkers, including blood eosinophils, FeNO, and total IgE, with median values all exceeding traditionally accepted cut points. Although patients with mucus plugging were receiving significantly higher ICS doses, and despite the suppressive effect of ICS on FeNO, they still had higher FeNO levels. “We therefore postulate that asthma patients with the MP phenotype might potentially experience greater treatment response to biologics targeting the underlying inflammatory endotype,” the investigators stated, adding that “the presence of mucus plugging should be recognized as a treatable trait for patients with severe asthma in terms of targeting therapy with biologics.”

They wrote that, “in a real-life clinic setting, the presence of mucus plugging detected on HRCT was associated with more severe exacerbations, more severe airflow obstruction, and greater T2 inflammation. This, in turn, suggests that imaging should be part of the routine workup of patients with poorly controlled severe asthma.”

In an accompanying editorial, Jorge Cedano, MD, Jiwoong Choi, PhD, and Mario Castro, MD, MPH, of the University of Kansas, Kansas City, cited that the prevalence and contribution of mucus plugging in the pathophysiology and morbidity of uncontrolled asthma is much greater than has been appreciated. They focused particularly on the suggestion that, even after adjusting for confounders, molds such as Apergillus may play a causal role, along with blood eosinophils, fractional exhaled nitric oxide, and total IgE, in T2 inflammation.

While current biologic therapies targeting the T2 phenotype have not yet been shown to reverse the progressive loss of lung function or lung remodeling process, the editorialists referenced a recent post hoc analysis of the CASCADE study showing mucus plugging reduction with the biologic tezepelumab versus placebo correlated with lung function improvement. “At least 20% of patients with moderate to severe asthma will experience progressive decline in lung function, more exacerbations, and worse asthma control despite the use of controller therapies. If physicians could identify the MP phenotype using computed tomography, then potentially earlier treatment with biologic therapy may improve asthma control and prevent future decline in lung function,” they said.

The study limitations listed included its retrospective observational nature and the fact that the study had only one senior thoracic radiologist interpreting the lung scans.

The study authors cited numerous conflicts of interest with pharmaceutical companies and medical societies. Dr. Castro reported affiliation or involvement in multiple organizations or entities with a financial or nonfinancial interest in the subject matter or materials discussed in the article.