Heidi Splete

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Baylor College of Medicine

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

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

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

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

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

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

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

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

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

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

Data may inform device decisions

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

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

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

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

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

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

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

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

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

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

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

Baylor College of Medicine

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

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

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

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

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

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

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

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

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

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

Data may inform device decisions

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

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

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

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

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

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

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

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

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

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

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

Baylor College of Medicine

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

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

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

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

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

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

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

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

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

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

Data may inform device decisions

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

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

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

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

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

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

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

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

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

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

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

New York-Presbyterian/Columbia University Irving Medical Center

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

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

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

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

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

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

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

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

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

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

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

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

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

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

New York-Presbyterian/Columbia University Irving Medical Center

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

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

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

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

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

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

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

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

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

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

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

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

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

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

New York-Presbyterian/Columbia University Irving Medical Center

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

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

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

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

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

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

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

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

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

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

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

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

TOPLINE:

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

METHODOLOGY:

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

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

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

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

TAKEAWAY:

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

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

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

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

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

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

TAKEAWAY:

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

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

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

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

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

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

TAKEAWAY:

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

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

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

BPaLM poised to improve TB care

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BPaLM poised to improve TB care

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BPaLM poised to improve TB care

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

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

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

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

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

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

Use of low-dose aspirin to manage hypertension in pregnancy caused no increased flares in patients with inflammatory bowel disease, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.

Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.

The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.

A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).

Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).

The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.

“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”

Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”

The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Reducing exposure to tobacco smoke may reduce the burden of chronic obstructive pulmonary disease, and public health measures are needed, according to a new Tobacco Knowledge Summary from the World Health Organization.

“Smoking is a major risk factor for COPD and leads to airway inflammation and remodeling associated with lung destruction,” and contributes to approximately 70% of COPD cases worldwide, according to the statement.

Types of tobacco exposure include not only traditional smoked tobacco products (cigarettes, cigars, pipes, water pipes, kreteks, and bidis), but also smokeless tobacco, heated tobacco products, and electronic nicotine delivery systems; the addition of chemicals and flavors can increase the appeal of tobacco products and promote addiction, the authors wrote. Hookahs and water pipes “are at least as detrimental to lung health as smoking cigarettes and should not be considered as a safe alternative,” they added.

The risk of COPD extends to new e-cigarette products, the authors noted. A study in the American Journal of Preventive Medicine showed that current users of e-cigarettes had a 75% increased risk of developing COPD compared with individuals who have never used e-cigarettes.

Individuals with COPD also face an increased risk of cardiovascular disease and type 2 diabetes, and smokers with COPD who quit not only improve their COPD but also reduce their risk of developing these conditions, the authors said.
 

Mechanism of action explored

The authors noted how tobacco smoking may cause COPD when inhaled particles are deposited through the airway.

Growing evidence suggests that extracellular vesicles may play a role in the development of lung disorders such as COPD, and cigarette smoke can have an impact through this channel. A study published in the American Journal of Respiratory and Critical Care Medicine offered evidence of a potential link between exposure to cigarette smoke and the generation of a unique extracellular vesicle population that could promote the development of lung damage. In the study, Matthew C. Madison, MD, of the University of Alabama, Birmingham, and colleagues examined activity in extracellular vesicles from the bronchoalveolar lavage (BAL) fluid of smoke-exposed mice and human smokers who were otherwise healthy.

The researchers found that airway extracellular vesicles in mice or humans exposed to cigarette smoke had the ability to cause rapid lung damage when transferred into naive recipient mice. The results provide a new model that can inform preclinical COPD research, they wrote.
 

Public health action needed

“In recognition of COPD and Lung Cancer Awareness Month, the World Health Organization (WHO) emphasizes the impact of various forms of tobacco use on COPD,” Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

“This article focuses on the different types of tobacco exposure, the health care burden associated with COPD, and the risk of developing lung cancer. It also addresses the high-risk groups, especially youth, underscoring the importance of public education and the implementation of restrictions on tobacco use to combat these growing concerns,” she said.

“Education, awareness, and targeted interventions are essential for smoking cessation and COPD management,” said Dr. Narendra. “These elements are key to informing the public about smoking risks, encouraging behavioral change, and ultimately reducing the incidence of smoking-related diseases,” she emphasized.

The WHO statement called for population-level interventions including brief advice to tobacco users, toll-free quit lines, pharmacological interventions, use of messaging and chatbots to provide quit support, and the WHO quit tobacco mobile app.

“It is imperative that all tobacco users, particularly those living in low- to middle-income countries, have access to comprehensive cessation support aligned with WHO recommendations,” the authors wrote.

Finally, the authors emphasized the need to protect children and teens from the dangers of tobacco use through product regulation and to expose the tobacco industry’s marketing tactics.

“The article offers a comprehensive look at different types of tobacco exposure and their contribution to the development of COPD,” Dr. Narendra told this news organization. “Notably, it presents groundbreaking evidence of a strong association between the use of electronic nicotine delivery systems (ENDS) and heated tobacco products to development of COPD; additionally, it provides valuable guidance on smoking cessation resources for physicians to help patients quit smoking,” she said.

Looking ahead, more research is needed on “developing and sustaining state-specific or population-specific interventions for effective smoking cessation programs, and reducing the burden of COPD,” Dr. Narendra said.

The study by Madison and colleagues was supported by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Science, the U.S. Veterans Affairs Administration, the Cystic Fibrosis Foundation Research Development Program, and the Veterans Affairs Merit grant.

Additional financial support came from Imperial College London, a Wellcome Trust Senior Research Fellowship, and Rosetrees Trust/The Stoneygate Trust.

Dr. Narendra had no financial conflicts to disclose but serves as a member of the editorial board of CHEST Physician.

Reducing exposure to tobacco smoke may reduce the burden of chronic obstructive pulmonary disease, and public health measures are needed, according to a new Tobacco Knowledge Summary from the World Health Organization.

“Smoking is a major risk factor for COPD and leads to airway inflammation and remodeling associated with lung destruction,” and contributes to approximately 70% of COPD cases worldwide, according to the statement.

Types of tobacco exposure include not only traditional smoked tobacco products (cigarettes, cigars, pipes, water pipes, kreteks, and bidis), but also smokeless tobacco, heated tobacco products, and electronic nicotine delivery systems; the addition of chemicals and flavors can increase the appeal of tobacco products and promote addiction, the authors wrote. Hookahs and water pipes “are at least as detrimental to lung health as smoking cigarettes and should not be considered as a safe alternative,” they added.

The risk of COPD extends to new e-cigarette products, the authors noted. A study in the American Journal of Preventive Medicine showed that current users of e-cigarettes had a 75% increased risk of developing COPD compared with individuals who have never used e-cigarettes.

Individuals with COPD also face an increased risk of cardiovascular disease and type 2 diabetes, and smokers with COPD who quit not only improve their COPD but also reduce their risk of developing these conditions, the authors said.
 

Mechanism of action explored

The authors noted how tobacco smoking may cause COPD when inhaled particles are deposited through the airway.

Growing evidence suggests that extracellular vesicles may play a role in the development of lung disorders such as COPD, and cigarette smoke can have an impact through this channel. A study published in the American Journal of Respiratory and Critical Care Medicine offered evidence of a potential link between exposure to cigarette smoke and the generation of a unique extracellular vesicle population that could promote the development of lung damage. In the study, Matthew C. Madison, MD, of the University of Alabama, Birmingham, and colleagues examined activity in extracellular vesicles from the bronchoalveolar lavage (BAL) fluid of smoke-exposed mice and human smokers who were otherwise healthy.

The researchers found that airway extracellular vesicles in mice or humans exposed to cigarette smoke had the ability to cause rapid lung damage when transferred into naive recipient mice. The results provide a new model that can inform preclinical COPD research, they wrote.
 

Public health action needed

“In recognition of COPD and Lung Cancer Awareness Month, the World Health Organization (WHO) emphasizes the impact of various forms of tobacco use on COPD,” Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

“This article focuses on the different types of tobacco exposure, the health care burden associated with COPD, and the risk of developing lung cancer. It also addresses the high-risk groups, especially youth, underscoring the importance of public education and the implementation of restrictions on tobacco use to combat these growing concerns,” she said.

“Education, awareness, and targeted interventions are essential for smoking cessation and COPD management,” said Dr. Narendra. “These elements are key to informing the public about smoking risks, encouraging behavioral change, and ultimately reducing the incidence of smoking-related diseases,” she emphasized.

The WHO statement called for population-level interventions including brief advice to tobacco users, toll-free quit lines, pharmacological interventions, use of messaging and chatbots to provide quit support, and the WHO quit tobacco mobile app.

“It is imperative that all tobacco users, particularly those living in low- to middle-income countries, have access to comprehensive cessation support aligned with WHO recommendations,” the authors wrote.

Finally, the authors emphasized the need to protect children and teens from the dangers of tobacco use through product regulation and to expose the tobacco industry’s marketing tactics.

“The article offers a comprehensive look at different types of tobacco exposure and their contribution to the development of COPD,” Dr. Narendra told this news organization. “Notably, it presents groundbreaking evidence of a strong association between the use of electronic nicotine delivery systems (ENDS) and heated tobacco products to development of COPD; additionally, it provides valuable guidance on smoking cessation resources for physicians to help patients quit smoking,” she said.

Looking ahead, more research is needed on “developing and sustaining state-specific or population-specific interventions for effective smoking cessation programs, and reducing the burden of COPD,” Dr. Narendra said.

The study by Madison and colleagues was supported by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Science, the U.S. Veterans Affairs Administration, the Cystic Fibrosis Foundation Research Development Program, and the Veterans Affairs Merit grant.

Additional financial support came from Imperial College London, a Wellcome Trust Senior Research Fellowship, and Rosetrees Trust/The Stoneygate Trust.

Dr. Narendra had no financial conflicts to disclose but serves as a member of the editorial board of CHEST Physician.

Reducing exposure to tobacco smoke may reduce the burden of chronic obstructive pulmonary disease, and public health measures are needed, according to a new Tobacco Knowledge Summary from the World Health Organization.

“Smoking is a major risk factor for COPD and leads to airway inflammation and remodeling associated with lung destruction,” and contributes to approximately 70% of COPD cases worldwide, according to the statement.

Types of tobacco exposure include not only traditional smoked tobacco products (cigarettes, cigars, pipes, water pipes, kreteks, and bidis), but also smokeless tobacco, heated tobacco products, and electronic nicotine delivery systems; the addition of chemicals and flavors can increase the appeal of tobacco products and promote addiction, the authors wrote. Hookahs and water pipes “are at least as detrimental to lung health as smoking cigarettes and should not be considered as a safe alternative,” they added.

The risk of COPD extends to new e-cigarette products, the authors noted. A study in the American Journal of Preventive Medicine showed that current users of e-cigarettes had a 75% increased risk of developing COPD compared with individuals who have never used e-cigarettes.

Individuals with COPD also face an increased risk of cardiovascular disease and type 2 diabetes, and smokers with COPD who quit not only improve their COPD but also reduce their risk of developing these conditions, the authors said.
 

Mechanism of action explored

The authors noted how tobacco smoking may cause COPD when inhaled particles are deposited through the airway.

Growing evidence suggests that extracellular vesicles may play a role in the development of lung disorders such as COPD, and cigarette smoke can have an impact through this channel. A study published in the American Journal of Respiratory and Critical Care Medicine offered evidence of a potential link between exposure to cigarette smoke and the generation of a unique extracellular vesicle population that could promote the development of lung damage. In the study, Matthew C. Madison, MD, of the University of Alabama, Birmingham, and colleagues examined activity in extracellular vesicles from the bronchoalveolar lavage (BAL) fluid of smoke-exposed mice and human smokers who were otherwise healthy.

The researchers found that airway extracellular vesicles in mice or humans exposed to cigarette smoke had the ability to cause rapid lung damage when transferred into naive recipient mice. The results provide a new model that can inform preclinical COPD research, they wrote.
 

Public health action needed

“In recognition of COPD and Lung Cancer Awareness Month, the World Health Organization (WHO) emphasizes the impact of various forms of tobacco use on COPD,” Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

“This article focuses on the different types of tobacco exposure, the health care burden associated with COPD, and the risk of developing lung cancer. It also addresses the high-risk groups, especially youth, underscoring the importance of public education and the implementation of restrictions on tobacco use to combat these growing concerns,” she said.

“Education, awareness, and targeted interventions are essential for smoking cessation and COPD management,” said Dr. Narendra. “These elements are key to informing the public about smoking risks, encouraging behavioral change, and ultimately reducing the incidence of smoking-related diseases,” she emphasized.

The WHO statement called for population-level interventions including brief advice to tobacco users, toll-free quit lines, pharmacological interventions, use of messaging and chatbots to provide quit support, and the WHO quit tobacco mobile app.

“It is imperative that all tobacco users, particularly those living in low- to middle-income countries, have access to comprehensive cessation support aligned with WHO recommendations,” the authors wrote.

Finally, the authors emphasized the need to protect children and teens from the dangers of tobacco use through product regulation and to expose the tobacco industry’s marketing tactics.

“The article offers a comprehensive look at different types of tobacco exposure and their contribution to the development of COPD,” Dr. Narendra told this news organization. “Notably, it presents groundbreaking evidence of a strong association between the use of electronic nicotine delivery systems (ENDS) and heated tobacco products to development of COPD; additionally, it provides valuable guidance on smoking cessation resources for physicians to help patients quit smoking,” she said.

Looking ahead, more research is needed on “developing and sustaining state-specific or population-specific interventions for effective smoking cessation programs, and reducing the burden of COPD,” Dr. Narendra said.

The study by Madison and colleagues was supported by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Science, the U.S. Veterans Affairs Administration, the Cystic Fibrosis Foundation Research Development Program, and the Veterans Affairs Merit grant.

Additional financial support came from Imperial College London, a Wellcome Trust Senior Research Fellowship, and Rosetrees Trust/The Stoneygate Trust.

Dr. Narendra had no financial conflicts to disclose but serves as a member of the editorial board of CHEST Physician.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

Women with bipolar disorder were three times more likely than were healthy controls to experience polycystic ovarian syndrome, based on data from nearly 250 individuals.

Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.

However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.

In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.

PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).

In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.

A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).

“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.

The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.

More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Women with bipolar disorder were three times more likely than were healthy controls to experience polycystic ovarian syndrome, based on data from nearly 250 individuals.

Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.

However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.

In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.

PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).

In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.

A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).

“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.

The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.

More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Women with bipolar disorder were three times more likely than were healthy controls to experience polycystic ovarian syndrome, based on data from nearly 250 individuals.

Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.

However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.

In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.

PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).

In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.

A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).

“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.

The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.

More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.