Ob.Gyn. News

Topical sildenafil (citrate) cream 3.6% used by healthy premenopausal women with a primary symptom of female sexual arousal disorder did not show statistically significant improvement over placebo in the coprimary or secondary endpoints over a 3-month period in new preliminary study data published in Obstetrics & Gynecology.

Topical sildenafil cream is currently used for erectile dysfunction in men. There are no US Food and Drug Administration–approved treatments for female sexual arousal disorder, which affects up to 26% of women in the United States by some estimates.

Isabella Johnson, senior manager of product development at Daré Bioscience, San Diego, California, led a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream’s potential to help women improve their sexual experiences.

The study included 200 women with female sexual arousal disorder randomized to sildenafil cream (n = 101) or placebo cream (n = 99); 177 completed the trial and made up the intention-to-treat group. Healthy premenopausal women at least 18 years old and their sexual partners were screened for the study.

The authors report that the primary endpoints were scores on Sexual Function Questionnaire (SFQ28) arousal sensation domain and question 14 on the Female Sexual Distress Scale — Desire/Arousal/Orgasm (FSD-DAO), which asks “How often in the past 30 days did you feel concerned by difficulties with sexual arousal?”  The secondary endpoint was the average number and average proportion of satisfactory sexual events. Topical sildenafil was not more effective than placebo with these primary or secondary endpoints.
 

Some Subgroups Benefited

However, a post hoc analysis told a different story. “[A]mong a subset of women with female sexual arousal disorder only or female sexual arousal disorder with concomitant decreased desire, we found either trends or significant improvements in sexual functioning with sildenafil cream compared with placebo cream across multiple aspects of sexual function,” the authors write.

The researchers also noted that several FSDS-DAO questions, other than question 14, asked about generalized feelings related to sexual distress and interpersonal difficulties and scores on those questions showed significant improvement with sildenafil cream compared with placebo in the exploratory subset.

“The total FSDS-DAO score decreased by about 7 points for sildenafil cream users in the subset population (a clinically meaningful decrease in sexual distress) compared with a two-point decrease for placebo cream users (P = .10),” they write.

Post Hoc Analysis Is Exploratory

JoAnn V. Pinkerton, MD, with the Department of Obstetrics and Gynecology, University of Virginia Health in Charlottesville, writes in an editorial that because the authors did not adjust for multiple hypothesis testing, the post hoc subset analyses should be considered only exploratory.

She notes that the trial was underpowered partly because it was halted after recruitment challenges during the COVID-19 pandemic. The small sample size and the varied reasons for arousal disorder among the women “may have limited the ability to find a positive outcome.”

The underlying mechanisms of female sexual arousal disorder are not well understood. But the study findings point to some groups that may benefit or likely will not benefit, Dr. Pinkerton writes.

“Because improvement in genital arousal is thought to be due to the increased genital blood flow from sildenafil citrate, the subset of participants found least likely to benefit from sildenafil citrate cream were those with concomitant orgasmic dysfunction with or without genital pain,” she writes.
 

Data May Inform Phase 3 Trial

This phase 2b trial sets the stage for a phase 3 trial, she writes, to evaluate sildenafil topical cream in women with female sexual arousal disorder in the subsets where there were positive findings (those with or without a secondary diagnosis of decreased desire) but not among women having difficulty reaching orgasm.

“If positive, it could lead to a new therapeutic area for the unmet treatment needs of premenopausal and postmenopausal women with female sexual arousal disorder,” Dr. Pinkerton writes.

A study coauthor, Clint Dart, reports money was paid to his institution from Daré Bioscience, he provided independent data verification, and he is an employee of Premier Research. Isabella Johnson, Andrea Ries Thurman, MD, Jessica Hatheway, MBA, David R. Friend, PhD, and Andrew Goldstein, MD, are employees of Daré Bioscience. Katherine A. Cornell is an employee of Strategic Science & Technologies, LLC. C. Paige Brainard, MD, was financially compensated by Del Sol Research Management and her practice received funding from Daré Bioscience for study-specific activities. Dr. Goldstein also reported receiving payments from Nuvig, Ipsen, and AbbVie. Dr. Pinkerton’s institution received funds from Bayer Pharmaceuticals as she served as PI for a multinational clinical trial.

Topical sildenafil (citrate) cream 3.6% used by healthy premenopausal women with a primary symptom of female sexual arousal disorder did not show statistically significant improvement over placebo in the coprimary or secondary endpoints over a 3-month period in new preliminary study data published in Obstetrics & Gynecology.

Topical sildenafil cream is currently used for erectile dysfunction in men. There are no US Food and Drug Administration–approved treatments for female sexual arousal disorder, which affects up to 26% of women in the United States by some estimates.

Isabella Johnson, senior manager of product development at Daré Bioscience, San Diego, California, led a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream’s potential to help women improve their sexual experiences.

The study included 200 women with female sexual arousal disorder randomized to sildenafil cream (n = 101) or placebo cream (n = 99); 177 completed the trial and made up the intention-to-treat group. Healthy premenopausal women at least 18 years old and their sexual partners were screened for the study.

The authors report that the primary endpoints were scores on Sexual Function Questionnaire (SFQ28) arousal sensation domain and question 14 on the Female Sexual Distress Scale — Desire/Arousal/Orgasm (FSD-DAO), which asks “How often in the past 30 days did you feel concerned by difficulties with sexual arousal?”  The secondary endpoint was the average number and average proportion of satisfactory sexual events. Topical sildenafil was not more effective than placebo with these primary or secondary endpoints.
 

Some Subgroups Benefited

However, a post hoc analysis told a different story. “[A]mong a subset of women with female sexual arousal disorder only or female sexual arousal disorder with concomitant decreased desire, we found either trends or significant improvements in sexual functioning with sildenafil cream compared with placebo cream across multiple aspects of sexual function,” the authors write.

The researchers also noted that several FSDS-DAO questions, other than question 14, asked about generalized feelings related to sexual distress and interpersonal difficulties and scores on those questions showed significant improvement with sildenafil cream compared with placebo in the exploratory subset.

“The total FSDS-DAO score decreased by about 7 points for sildenafil cream users in the subset population (a clinically meaningful decrease in sexual distress) compared with a two-point decrease for placebo cream users (P = .10),” they write.

Post Hoc Analysis Is Exploratory

JoAnn V. Pinkerton, MD, with the Department of Obstetrics and Gynecology, University of Virginia Health in Charlottesville, writes in an editorial that because the authors did not adjust for multiple hypothesis testing, the post hoc subset analyses should be considered only exploratory.

She notes that the trial was underpowered partly because it was halted after recruitment challenges during the COVID-19 pandemic. The small sample size and the varied reasons for arousal disorder among the women “may have limited the ability to find a positive outcome.”

The underlying mechanisms of female sexual arousal disorder are not well understood. But the study findings point to some groups that may benefit or likely will not benefit, Dr. Pinkerton writes.

“Because improvement in genital arousal is thought to be due to the increased genital blood flow from sildenafil citrate, the subset of participants found least likely to benefit from sildenafil citrate cream were those with concomitant orgasmic dysfunction with or without genital pain,” she writes.
 

Data May Inform Phase 3 Trial

This phase 2b trial sets the stage for a phase 3 trial, she writes, to evaluate sildenafil topical cream in women with female sexual arousal disorder in the subsets where there were positive findings (those with or without a secondary diagnosis of decreased desire) but not among women having difficulty reaching orgasm.

“If positive, it could lead to a new therapeutic area for the unmet treatment needs of premenopausal and postmenopausal women with female sexual arousal disorder,” Dr. Pinkerton writes.

A study coauthor, Clint Dart, reports money was paid to his institution from Daré Bioscience, he provided independent data verification, and he is an employee of Premier Research. Isabella Johnson, Andrea Ries Thurman, MD, Jessica Hatheway, MBA, David R. Friend, PhD, and Andrew Goldstein, MD, are employees of Daré Bioscience. Katherine A. Cornell is an employee of Strategic Science & Technologies, LLC. C. Paige Brainard, MD, was financially compensated by Del Sol Research Management and her practice received funding from Daré Bioscience for study-specific activities. Dr. Goldstein also reported receiving payments from Nuvig, Ipsen, and AbbVie. Dr. Pinkerton’s institution received funds from Bayer Pharmaceuticals as she served as PI for a multinational clinical trial.

Topical sildenafil (citrate) cream 3.6% used by healthy premenopausal women with a primary symptom of female sexual arousal disorder did not show statistically significant improvement over placebo in the coprimary or secondary endpoints over a 3-month period in new preliminary study data published in Obstetrics & Gynecology.

Topical sildenafil cream is currently used for erectile dysfunction in men. There are no US Food and Drug Administration–approved treatments for female sexual arousal disorder, which affects up to 26% of women in the United States by some estimates.

Isabella Johnson, senior manager of product development at Daré Bioscience, San Diego, California, led a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream’s potential to help women improve their sexual experiences.

The study included 200 women with female sexual arousal disorder randomized to sildenafil cream (n = 101) or placebo cream (n = 99); 177 completed the trial and made up the intention-to-treat group. Healthy premenopausal women at least 18 years old and their sexual partners were screened for the study.

The authors report that the primary endpoints were scores on Sexual Function Questionnaire (SFQ28) arousal sensation domain and question 14 on the Female Sexual Distress Scale — Desire/Arousal/Orgasm (FSD-DAO), which asks “How often in the past 30 days did you feel concerned by difficulties with sexual arousal?”  The secondary endpoint was the average number and average proportion of satisfactory sexual events. Topical sildenafil was not more effective than placebo with these primary or secondary endpoints.
 

Some Subgroups Benefited

However, a post hoc analysis told a different story. “[A]mong a subset of women with female sexual arousal disorder only or female sexual arousal disorder with concomitant decreased desire, we found either trends or significant improvements in sexual functioning with sildenafil cream compared with placebo cream across multiple aspects of sexual function,” the authors write.

The researchers also noted that several FSDS-DAO questions, other than question 14, asked about generalized feelings related to sexual distress and interpersonal difficulties and scores on those questions showed significant improvement with sildenafil cream compared with placebo in the exploratory subset.

“The total FSDS-DAO score decreased by about 7 points for sildenafil cream users in the subset population (a clinically meaningful decrease in sexual distress) compared with a two-point decrease for placebo cream users (P = .10),” they write.

Post Hoc Analysis Is Exploratory

JoAnn V. Pinkerton, MD, with the Department of Obstetrics and Gynecology, University of Virginia Health in Charlottesville, writes in an editorial that because the authors did not adjust for multiple hypothesis testing, the post hoc subset analyses should be considered only exploratory.

She notes that the trial was underpowered partly because it was halted after recruitment challenges during the COVID-19 pandemic. The small sample size and the varied reasons for arousal disorder among the women “may have limited the ability to find a positive outcome.”

The underlying mechanisms of female sexual arousal disorder are not well understood. But the study findings point to some groups that may benefit or likely will not benefit, Dr. Pinkerton writes.

“Because improvement in genital arousal is thought to be due to the increased genital blood flow from sildenafil citrate, the subset of participants found least likely to benefit from sildenafil citrate cream were those with concomitant orgasmic dysfunction with or without genital pain,” she writes.
 

Data May Inform Phase 3 Trial

This phase 2b trial sets the stage for a phase 3 trial, she writes, to evaluate sildenafil topical cream in women with female sexual arousal disorder in the subsets where there were positive findings (those with or without a secondary diagnosis of decreased desire) but not among women having difficulty reaching orgasm.

“If positive, it could lead to a new therapeutic area for the unmet treatment needs of premenopausal and postmenopausal women with female sexual arousal disorder,” Dr. Pinkerton writes.

A study coauthor, Clint Dart, reports money was paid to his institution from Daré Bioscience, he provided independent data verification, and he is an employee of Premier Research. Isabella Johnson, Andrea Ries Thurman, MD, Jessica Hatheway, MBA, David R. Friend, PhD, and Andrew Goldstein, MD, are employees of Daré Bioscience. Katherine A. Cornell is an employee of Strategic Science & Technologies, LLC. C. Paige Brainard, MD, was financially compensated by Del Sol Research Management and her practice received funding from Daré Bioscience for study-specific activities. Dr. Goldstein also reported receiving payments from Nuvig, Ipsen, and AbbVie. Dr. Pinkerton’s institution received funds from Bayer Pharmaceuticals as she served as PI for a multinational clinical trial.

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

TOPLINE:

Patients with pure mucinous breast cancer (PMBC) show superior recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), compared with patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Patients with PMBC had a 5-year RFI of 96.1%, RFS of 94.9%, and OS of 98.1%.

METHODOLOGY:

• Researchers analyzed data from 23,102 women diagnosed with hormone receptor–positive HER2-negative stage I-III breast cancer, including 20,684 with IDC, 1475 with ILC, and 943 with PMBC.
• The multicenter cohort study included patients who underwent primary breast surgery at six academic institutions in Singapore, Taiwan, Korea, and Japan between January 2000 and December 2015.
• Current National Comprehensive Cancer Network Clinical Practice Guidelines “recommend consideration of adjuvant chemotherapy only for node-positive tumors,” whereas adjuvant endocrine therapy is recommended for estrogen receptor–positive and/or progesterone receptor–positive, node-positive tumors or tumors ≥ 3 cm. Previous studies have reported no significant association between adjuvant chemotherapy and breast cancer–specific survival or OS in patients with early-stage mucinous breast carcinoma.
• The study aimed to compare the recurrence and survival outcomes of PMBC against IDC and ILC, identify clinicopathologic prognostic factors of PMBC, and explore the association of adjuvant systemic therapy with outcomes across subgroups of PMBC.
• Extracted information included patient demographics, tumor characteristics, treatment administered, and staging according to the AJCC TNM classifications.

TAKEAWAY:

• Patients with PMBC had better RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) than patients with IDC in multivariable Cox regression analyses.
• Fewer than half (48.7%) of the recurrences in patients with PMBC were distant, which was a lower rate than for patients with IDC (67.3%) and ILC (80.6%).
• Significant prognostic factors for RFI in PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70).
• No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age.

IN PRACTICE:

“This international multicenter cohort study on PMBC evaluated one of the largest contemporary real-world datasets for clinical prognostic factors, which also includes valuable data on relapse events, associations of adjuvant systemic therapy, and a comparison with the SEER database,” wrote the authors of the study. “In our cohort, as anticipated, PMBC showed superior RFI, RFS, and OS compared with IDC and ILC, which both had comparatively similar survival outcomes.”

SOURCE:

Corresponding author, Yoon-Sim Yap, MBBS, PhD, of the National Cancer Centre Singapore in Singapore, designed the study. The paper was published online on May 14 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature over a long period and lack of a central pathology review in this study are among its limitations. The high extent of missing values for tumor grade in PMBC in the multicenter cohort could impact the identified prognostic factors. The study’s findings may not be generalizable to all populations due to the specific geographic locations of the participating institutions.

DISCLOSURES:

Study author Yeon Hee Park, MD, PhD, disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi Sankyo and serving as a consultant for AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, Merck, Eisai, Roche, Daiichi Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with pure mucinous breast cancer (PMBC) show superior recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), compared with patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Patients with PMBC had a 5-year RFI of 96.1%, RFS of 94.9%, and OS of 98.1%.

METHODOLOGY:

• Researchers analyzed data from 23,102 women diagnosed with hormone receptor–positive HER2-negative stage I-III breast cancer, including 20,684 with IDC, 1475 with ILC, and 943 with PMBC.
• The multicenter cohort study included patients who underwent primary breast surgery at six academic institutions in Singapore, Taiwan, Korea, and Japan between January 2000 and December 2015.
• Current National Comprehensive Cancer Network Clinical Practice Guidelines “recommend consideration of adjuvant chemotherapy only for node-positive tumors,” whereas adjuvant endocrine therapy is recommended for estrogen receptor–positive and/or progesterone receptor–positive, node-positive tumors or tumors ≥ 3 cm. Previous studies have reported no significant association between adjuvant chemotherapy and breast cancer–specific survival or OS in patients with early-stage mucinous breast carcinoma.
• The study aimed to compare the recurrence and survival outcomes of PMBC against IDC and ILC, identify clinicopathologic prognostic factors of PMBC, and explore the association of adjuvant systemic therapy with outcomes across subgroups of PMBC.
• Extracted information included patient demographics, tumor characteristics, treatment administered, and staging according to the AJCC TNM classifications.

TAKEAWAY:

• Patients with PMBC had better RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) than patients with IDC in multivariable Cox regression analyses.
• Fewer than half (48.7%) of the recurrences in patients with PMBC were distant, which was a lower rate than for patients with IDC (67.3%) and ILC (80.6%).
• Significant prognostic factors for RFI in PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70).
• No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age.

IN PRACTICE:

“This international multicenter cohort study on PMBC evaluated one of the largest contemporary real-world datasets for clinical prognostic factors, which also includes valuable data on relapse events, associations of adjuvant systemic therapy, and a comparison with the SEER database,” wrote the authors of the study. “In our cohort, as anticipated, PMBC showed superior RFI, RFS, and OS compared with IDC and ILC, which both had comparatively similar survival outcomes.”

SOURCE:

Corresponding author, Yoon-Sim Yap, MBBS, PhD, of the National Cancer Centre Singapore in Singapore, designed the study. The paper was published online on May 14 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature over a long period and lack of a central pathology review in this study are among its limitations. The high extent of missing values for tumor grade in PMBC in the multicenter cohort could impact the identified prognostic factors. The study’s findings may not be generalizable to all populations due to the specific geographic locations of the participating institutions.

DISCLOSURES:

Study author Yeon Hee Park, MD, PhD, disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi Sankyo and serving as a consultant for AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, Merck, Eisai, Roche, Daiichi Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with pure mucinous breast cancer (PMBC) show superior recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), compared with patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Patients with PMBC had a 5-year RFI of 96.1%, RFS of 94.9%, and OS of 98.1%.

METHODOLOGY:

• Researchers analyzed data from 23,102 women diagnosed with hormone receptor–positive HER2-negative stage I-III breast cancer, including 20,684 with IDC, 1475 with ILC, and 943 with PMBC.
• The multicenter cohort study included patients who underwent primary breast surgery at six academic institutions in Singapore, Taiwan, Korea, and Japan between January 2000 and December 2015.
• Current National Comprehensive Cancer Network Clinical Practice Guidelines “recommend consideration of adjuvant chemotherapy only for node-positive tumors,” whereas adjuvant endocrine therapy is recommended for estrogen receptor–positive and/or progesterone receptor–positive, node-positive tumors or tumors ≥ 3 cm. Previous studies have reported no significant association between adjuvant chemotherapy and breast cancer–specific survival or OS in patients with early-stage mucinous breast carcinoma.
• The study aimed to compare the recurrence and survival outcomes of PMBC against IDC and ILC, identify clinicopathologic prognostic factors of PMBC, and explore the association of adjuvant systemic therapy with outcomes across subgroups of PMBC.
• Extracted information included patient demographics, tumor characteristics, treatment administered, and staging according to the AJCC TNM classifications.

TAKEAWAY:

• Patients with PMBC had better RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) than patients with IDC in multivariable Cox regression analyses.
• Fewer than half (48.7%) of the recurrences in patients with PMBC were distant, which was a lower rate than for patients with IDC (67.3%) and ILC (80.6%).
• Significant prognostic factors for RFI in PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70).
• No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age.

IN PRACTICE:

“This international multicenter cohort study on PMBC evaluated one of the largest contemporary real-world datasets for clinical prognostic factors, which also includes valuable data on relapse events, associations of adjuvant systemic therapy, and a comparison with the SEER database,” wrote the authors of the study. “In our cohort, as anticipated, PMBC showed superior RFI, RFS, and OS compared with IDC and ILC, which both had comparatively similar survival outcomes.”

SOURCE:

Corresponding author, Yoon-Sim Yap, MBBS, PhD, of the National Cancer Centre Singapore in Singapore, designed the study. The paper was published online on May 14 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature over a long period and lack of a central pathology review in this study are among its limitations. The high extent of missing values for tumor grade in PMBC in the multicenter cohort could impact the identified prognostic factors. The study’s findings may not be generalizable to all populations due to the specific geographic locations of the participating institutions.

DISCLOSURES:

Study author Yeon Hee Park, MD, PhD, disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi Sankyo and serving as a consultant for AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, Merck, Eisai, Roche, Daiichi Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Despite federal legislation improving healthcare access, concerted efforts are still needed to increase evidence-based treatment for maternal perinatal mental health issues, a large study of commercially insured mothers suggested. It found that federal legislation had variable and suboptimal effect on mental health services use by delivering mothers.

In the cross-sectional study, published in JAMA Network Open, psychotherapy receipt increased somewhat during 2007-2019 among all mothers and among those diagnosed with perinatal mood and anxiety disorders (PMADs). The timeline encompassed periods before and after passage of the Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008 and the Patient Protection and Affordable Care Act (ACA) of 2010.

The investigators, led by Kara Zivin, PhD, MS, MFA, a professor of psychiatry in the University of Michigan’s School of Public Health at Ann Arbor, found the results varied by policy and between the overall delivering population and the PMAD population. “We did not find a statistically significant immediate change associated with the MHPAEA or ACA in the overall delivering population, except for a steady increase in delivering women who received any psychotherapy after ACA,” Dr. Zivin and colleagues wrote.

The researchers looked at private insurance data for 837,316 deliveries among 716,052 women (64.2% White), ages 15-44 (mean 31.2), to assess changes in psychotherapy visits in the year before and after delivery. They also estimated per-visit out-of-pocket costs for the ACA in 2014 and the MHPAEA in 2010.

In the PMAD population, the MHPAEA was associated with an immediate increase in psychotherapy receipt of 0.72% (95% CI, 0.26%-1.18%; P = .002), followed by a sustained decrease of 0.05% (95% CI, 0.09%-0.02%; P = .001).

In both populations, the ACA was associated with immediate and sustained monthly increases in use of 0.77% (95% CI, 0.26%-1.27%; P = .003) and 0.07% (95% CI, 0.02%-0.12%; P = .005), respectively.

Post MHPAEA, both populations experienced a slight decrease in per-visit monthly out-of-pocket costs, while after the ACA they saw an immediate and steady monthly increase in these.

Although both policies expanded access to any psychotherapy, the greater number of people receiving visits coincided with fewer visits per person, the authors noted. “One hypothesis suggests that the number of available mental health clinicians may not have increased enough to meet the new demand; future research should better characterize this trend,” they wrote.

In addition, a lower standard cost per visit may have dampened the incentive to increase the number of mental health clinicians, they conjectured. These factors could explain why the PMAD group appeared to experience a decrease in the proportion receiving any psychotherapy after the MHPAEA’s implementation.

The findings should be reviewed in the context of the current mental health burden, the authors wrote, in which the shortage of mental health professionals means that less than 30% of mental healthcare needs are being met.

They called for more measures to mitigate the excess burden of PMADs.

This study was funded by the National Institutes of Health. Dr. Zivin had no conflicts of interest. Coauthor Dr. Dalton reported personal fees from Merck, the Society of Family Planning, Up to Date, and The Medical Letter outside of the submitted work.

Despite federal legislation improving healthcare access, concerted efforts are still needed to increase evidence-based treatment for maternal perinatal mental health issues, a large study of commercially insured mothers suggested. It found that federal legislation had variable and suboptimal effect on mental health services use by delivering mothers.

In the cross-sectional study, published in JAMA Network Open, psychotherapy receipt increased somewhat during 2007-2019 among all mothers and among those diagnosed with perinatal mood and anxiety disorders (PMADs). The timeline encompassed periods before and after passage of the Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008 and the Patient Protection and Affordable Care Act (ACA) of 2010.

The investigators, led by Kara Zivin, PhD, MS, MFA, a professor of psychiatry in the University of Michigan’s School of Public Health at Ann Arbor, found the results varied by policy and between the overall delivering population and the PMAD population. “We did not find a statistically significant immediate change associated with the MHPAEA or ACA in the overall delivering population, except for a steady increase in delivering women who received any psychotherapy after ACA,” Dr. Zivin and colleagues wrote.

The researchers looked at private insurance data for 837,316 deliveries among 716,052 women (64.2% White), ages 15-44 (mean 31.2), to assess changes in psychotherapy visits in the year before and after delivery. They also estimated per-visit out-of-pocket costs for the ACA in 2014 and the MHPAEA in 2010.

In the PMAD population, the MHPAEA was associated with an immediate increase in psychotherapy receipt of 0.72% (95% CI, 0.26%-1.18%; P = .002), followed by a sustained decrease of 0.05% (95% CI, 0.09%-0.02%; P = .001).

In both populations, the ACA was associated with immediate and sustained monthly increases in use of 0.77% (95% CI, 0.26%-1.27%; P = .003) and 0.07% (95% CI, 0.02%-0.12%; P = .005), respectively.

Post MHPAEA, both populations experienced a slight decrease in per-visit monthly out-of-pocket costs, while after the ACA they saw an immediate and steady monthly increase in these.

Although both policies expanded access to any psychotherapy, the greater number of people receiving visits coincided with fewer visits per person, the authors noted. “One hypothesis suggests that the number of available mental health clinicians may not have increased enough to meet the new demand; future research should better characterize this trend,” they wrote.

In addition, a lower standard cost per visit may have dampened the incentive to increase the number of mental health clinicians, they conjectured. These factors could explain why the PMAD group appeared to experience a decrease in the proportion receiving any psychotherapy after the MHPAEA’s implementation.

The findings should be reviewed in the context of the current mental health burden, the authors wrote, in which the shortage of mental health professionals means that less than 30% of mental healthcare needs are being met.

They called for more measures to mitigate the excess burden of PMADs.

This study was funded by the National Institutes of Health. Dr. Zivin had no conflicts of interest. Coauthor Dr. Dalton reported personal fees from Merck, the Society of Family Planning, Up to Date, and The Medical Letter outside of the submitted work.

Despite federal legislation improving healthcare access, concerted efforts are still needed to increase evidence-based treatment for maternal perinatal mental health issues, a large study of commercially insured mothers suggested. It found that federal legislation had variable and suboptimal effect on mental health services use by delivering mothers.

In the cross-sectional study, published in JAMA Network Open, psychotherapy receipt increased somewhat during 2007-2019 among all mothers and among those diagnosed with perinatal mood and anxiety disorders (PMADs). The timeline encompassed periods before and after passage of the Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008 and the Patient Protection and Affordable Care Act (ACA) of 2010.

The investigators, led by Kara Zivin, PhD, MS, MFA, a professor of psychiatry in the University of Michigan’s School of Public Health at Ann Arbor, found the results varied by policy and between the overall delivering population and the PMAD population. “We did not find a statistically significant immediate change associated with the MHPAEA or ACA in the overall delivering population, except for a steady increase in delivering women who received any psychotherapy after ACA,” Dr. Zivin and colleagues wrote.

The researchers looked at private insurance data for 837,316 deliveries among 716,052 women (64.2% White), ages 15-44 (mean 31.2), to assess changes in psychotherapy visits in the year before and after delivery. They also estimated per-visit out-of-pocket costs for the ACA in 2014 and the MHPAEA in 2010.

In the PMAD population, the MHPAEA was associated with an immediate increase in psychotherapy receipt of 0.72% (95% CI, 0.26%-1.18%; P = .002), followed by a sustained decrease of 0.05% (95% CI, 0.09%-0.02%; P = .001).

In both populations, the ACA was associated with immediate and sustained monthly increases in use of 0.77% (95% CI, 0.26%-1.27%; P = .003) and 0.07% (95% CI, 0.02%-0.12%; P = .005), respectively.

Post MHPAEA, both populations experienced a slight decrease in per-visit monthly out-of-pocket costs, while after the ACA they saw an immediate and steady monthly increase in these.

Although both policies expanded access to any psychotherapy, the greater number of people receiving visits coincided with fewer visits per person, the authors noted. “One hypothesis suggests that the number of available mental health clinicians may not have increased enough to meet the new demand; future research should better characterize this trend,” they wrote.

In addition, a lower standard cost per visit may have dampened the incentive to increase the number of mental health clinicians, they conjectured. These factors could explain why the PMAD group appeared to experience a decrease in the proportion receiving any psychotherapy after the MHPAEA’s implementation.

The findings should be reviewed in the context of the current mental health burden, the authors wrote, in which the shortage of mental health professionals means that less than 30% of mental healthcare needs are being met.

They called for more measures to mitigate the excess burden of PMADs.

This study was funded by the National Institutes of Health. Dr. Zivin had no conflicts of interest. Coauthor Dr. Dalton reported personal fees from Merck, the Society of Family Planning, Up to Date, and The Medical Letter outside of the submitted work.

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

TOPLINE:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A systematic review and network meta-analysis found cranberry juice can help prevent urinary tract infections (UTIs).

METHODOLOGY:

• With an increasing prevalence of antimicrobial resistance and over 50% women reporting at least one episode of UTI each year, identifying evidence supporting possible nondrug interventions is necessary, according to the study researchers from Bond University, the University of Helsinki, and the University of Oxford.
• The primary study outcome was number of UTIs in each treatment or placebo group; the secondary outcomes were UTI symptoms such as increased bladder sensation, urgency, frequency, dysuria, and consumption of antimicrobial drugs.
• Studies analyzed included people of any age and gender at a risk for UTI.
• Researchers included 3091 participants from 18 randomized controlled trials and two nonrandomized controlled trials.

TAKEAWAY:

• Studies used one of the following interventions: Cranberry nonliquid products (tablet, capsule, or fruit), cranberry liquid, liquid other than cranberry, and no treatment.
• A total of 18 studies showed a 27% lower rate of UTIs with the consumption of cranberry juice than with placebo liquid (moderate certainty evidence) and a 54% lower rate of UTIs with the consumption of cranberry juice than with no treatment (very low certainty evidence).
• Based on a meta-analysis of six studies, antibiotic use was 49% lower with the consumption of cranberry juice than with placebo liquid and 59% lower than with no treatment.
• Cranberry compounds also were associated with a decrease in prevalence of UTI symptoms.

IN PRACTICE:

“The evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids benefit the rate of UTIs and reduce antibiotic use, and cranberry compounds benefit symptoms of infection, the combination of these, in cranberry juice, provides clear and significant clinical outcomes for the reduction in UTIs and antibiotic use and should be considered for the management of UTIs,” the authors wrote.

SOURCE:

The study was led by Christian Moro, PhD, faculty of health sciences and medicine at Bond University in Gold Coast, Australia, and was published online in European Urology Focus on July 18, 2024.

LIMITATIONS:

The authors noted that some planned findings such as the impact on antibiotic use were reduced due to limited studies. Some studies on cranberry tablets also provided education with the intervention, which could have affected UTI recurrence rates. Nearly all the 20 studies that were analyzed included mostly women; thus, comparisons between genders were not possible.

DISCLOSURES:

Dr. Moro reported no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A systematic review and network meta-analysis found cranberry juice can help prevent urinary tract infections (UTIs).

METHODOLOGY:

• With an increasing prevalence of antimicrobial resistance and over 50% women reporting at least one episode of UTI each year, identifying evidence supporting possible nondrug interventions is necessary, according to the study researchers from Bond University, the University of Helsinki, and the University of Oxford.
• The primary study outcome was number of UTIs in each treatment or placebo group; the secondary outcomes were UTI symptoms such as increased bladder sensation, urgency, frequency, dysuria, and consumption of antimicrobial drugs.
• Studies analyzed included people of any age and gender at a risk for UTI.
• Researchers included 3091 participants from 18 randomized controlled trials and two nonrandomized controlled trials.

TAKEAWAY:

• Studies used one of the following interventions: Cranberry nonliquid products (tablet, capsule, or fruit), cranberry liquid, liquid other than cranberry, and no treatment.
• A total of 18 studies showed a 27% lower rate of UTIs with the consumption of cranberry juice than with placebo liquid (moderate certainty evidence) and a 54% lower rate of UTIs with the consumption of cranberry juice than with no treatment (very low certainty evidence).
• Based on a meta-analysis of six studies, antibiotic use was 49% lower with the consumption of cranberry juice than with placebo liquid and 59% lower than with no treatment.
• Cranberry compounds also were associated with a decrease in prevalence of UTI symptoms.

IN PRACTICE:

“The evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids benefit the rate of UTIs and reduce antibiotic use, and cranberry compounds benefit symptoms of infection, the combination of these, in cranberry juice, provides clear and significant clinical outcomes for the reduction in UTIs and antibiotic use and should be considered for the management of UTIs,” the authors wrote.

SOURCE:

The study was led by Christian Moro, PhD, faculty of health sciences and medicine at Bond University in Gold Coast, Australia, and was published online in European Urology Focus on July 18, 2024.

LIMITATIONS:

The authors noted that some planned findings such as the impact on antibiotic use were reduced due to limited studies. Some studies on cranberry tablets also provided education with the intervention, which could have affected UTI recurrence rates. Nearly all the 20 studies that were analyzed included mostly women; thus, comparisons between genders were not possible.

DISCLOSURES:

Dr. Moro reported no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A systematic review and network meta-analysis found cranberry juice can help prevent urinary tract infections (UTIs).

METHODOLOGY:

• With an increasing prevalence of antimicrobial resistance and over 50% women reporting at least one episode of UTI each year, identifying evidence supporting possible nondrug interventions is necessary, according to the study researchers from Bond University, the University of Helsinki, and the University of Oxford.
• The primary study outcome was number of UTIs in each treatment or placebo group; the secondary outcomes were UTI symptoms such as increased bladder sensation, urgency, frequency, dysuria, and consumption of antimicrobial drugs.
• Studies analyzed included people of any age and gender at a risk for UTI.
• Researchers included 3091 participants from 18 randomized controlled trials and two nonrandomized controlled trials.

TAKEAWAY:

• Studies used one of the following interventions: Cranberry nonliquid products (tablet, capsule, or fruit), cranberry liquid, liquid other than cranberry, and no treatment.
• A total of 18 studies showed a 27% lower rate of UTIs with the consumption of cranberry juice than with placebo liquid (moderate certainty evidence) and a 54% lower rate of UTIs with the consumption of cranberry juice than with no treatment (very low certainty evidence).
• Based on a meta-analysis of six studies, antibiotic use was 49% lower with the consumption of cranberry juice than with placebo liquid and 59% lower than with no treatment.
• Cranberry compounds also were associated with a decrease in prevalence of UTI symptoms.

IN PRACTICE:

“The evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids benefit the rate of UTIs and reduce antibiotic use, and cranberry compounds benefit symptoms of infection, the combination of these, in cranberry juice, provides clear and significant clinical outcomes for the reduction in UTIs and antibiotic use and should be considered for the management of UTIs,” the authors wrote.

SOURCE:

The study was led by Christian Moro, PhD, faculty of health sciences and medicine at Bond University in Gold Coast, Australia, and was published online in European Urology Focus on July 18, 2024.

LIMITATIONS:

The authors noted that some planned findings such as the impact on antibiotic use were reduced due to limited studies. Some studies on cranberry tablets also provided education with the intervention, which could have affected UTI recurrence rates. Nearly all the 20 studies that were analyzed included mostly women; thus, comparisons between genders were not possible.

DISCLOSURES:

Dr. Moro reported no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Young and adult children of mothers with type 1 diabetes are almost half as likely be diagnosed with this condition compared with those with affected fathers, even with a similar genetic risk score. 

METHODOLOGY:

• Individuals with a family history of type 1 diabetes face 8-15 times higher risk for this condition than the general population, with the risk of inheritance from mothers with type 1 diabetes being about half that of fathers with type 1 diabetes; however, it is unclear if the effect continues past childhood and what is responsible for the difference in risk.
• Researchers performed a meta-analysis across five cohort studies involving 11,475 individuals diagnosed with type 1 diabetes aged 0-88 years to evaluate if maternal type 1 diabetes conferred relative protection only to young children.
• They compared the proportion of individuals with type 1 diabetes with affected fathers versus mothers and explored if this comparison was altered by the age at diagnosis and the timing of parental diagnosis relative to the birth of the offspring.
• Lastly, the inherited genetic risk for type 1 diabetes was compared between those with affected mothers versus fathers using a risk score composed of more than 60 different gene variants associated with type 1 diabetes.

TAKEAWAY:

• Individuals with type 1 diabetes were almost twice as likely to have a father with the condition than a mother (odds ratio, 1.79; P < .0001).
• The protective effect of maternal diabetes was seen regardless of whether the individuals were diagnosed with type 1 diabetes before or after age 18 years (P < .0001).
• Maternal diabetes was linked to a lower risk for type 1 diabetes in children only if the mother had type 1 diabetes during pregnancy.
• The genetic risk score for type 1 diabetes was not significantly different between those with affected fathers versus mothers (P = .31).

IN PRACTICE:

“Understanding why having a mother compared with a father with type 1 diabetes offers a relative protection against type 1 diabetes could help us develop new ways to prevent type 1 diabetes, such as treatments that mimic some of the protective elements from mothers,” study author Lowri Allen, MBChB, said in a news release.

SOURCE:

The study was led by Dr. Allen from the Diabetes Research Group, Cardiff University, Cardiff, Wales, and was published as an early release from the annual meeting of the European Association for the Study of Diabetes. 

LIMITATIONS:

This abstract did not discuss any limitations. The number of individuals and parents with type 1 diabetes in the meta-analysis was not disclosed. The baseline risk for type 1 diabetes among individuals with a mother, father, or both or no parent with type 1 diabetes was not disclosed. The number of people with type 1 diabetes under and over age 18 was not disclosed, nor were the numbers of mothers and fathers with type 1 diabetes. The relative risk in individuals having no parent with type 1 diabetes was not disclosed. Moreover, the race and ethnicity of the study populations were not disclosed. 

DISCLOSURES:

The Wellcome Trust supported this study. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Young and adult children of mothers with type 1 diabetes are almost half as likely be diagnosed with this condition compared with those with affected fathers, even with a similar genetic risk score. 

METHODOLOGY:

• Individuals with a family history of type 1 diabetes face 8-15 times higher risk for this condition than the general population, with the risk of inheritance from mothers with type 1 diabetes being about half that of fathers with type 1 diabetes; however, it is unclear if the effect continues past childhood and what is responsible for the difference in risk.
• Researchers performed a meta-analysis across five cohort studies involving 11,475 individuals diagnosed with type 1 diabetes aged 0-88 years to evaluate if maternal type 1 diabetes conferred relative protection only to young children.
• They compared the proportion of individuals with type 1 diabetes with affected fathers versus mothers and explored if this comparison was altered by the age at diagnosis and the timing of parental diagnosis relative to the birth of the offspring.
• Lastly, the inherited genetic risk for type 1 diabetes was compared between those with affected mothers versus fathers using a risk score composed of more than 60 different gene variants associated with type 1 diabetes.

TAKEAWAY:

• Individuals with type 1 diabetes were almost twice as likely to have a father with the condition than a mother (odds ratio, 1.79; P < .0001).
• The protective effect of maternal diabetes was seen regardless of whether the individuals were diagnosed with type 1 diabetes before or after age 18 years (P < .0001).
• Maternal diabetes was linked to a lower risk for type 1 diabetes in children only if the mother had type 1 diabetes during pregnancy.
• The genetic risk score for type 1 diabetes was not significantly different between those with affected fathers versus mothers (P = .31).

IN PRACTICE:

“Understanding why having a mother compared with a father with type 1 diabetes offers a relative protection against type 1 diabetes could help us develop new ways to prevent type 1 diabetes, such as treatments that mimic some of the protective elements from mothers,” study author Lowri Allen, MBChB, said in a news release.

SOURCE:

The study was led by Dr. Allen from the Diabetes Research Group, Cardiff University, Cardiff, Wales, and was published as an early release from the annual meeting of the European Association for the Study of Diabetes. 

LIMITATIONS:

This abstract did not discuss any limitations. The number of individuals and parents with type 1 diabetes in the meta-analysis was not disclosed. The baseline risk for type 1 diabetes among individuals with a mother, father, or both or no parent with type 1 diabetes was not disclosed. The number of people with type 1 diabetes under and over age 18 was not disclosed, nor were the numbers of mothers and fathers with type 1 diabetes. The relative risk in individuals having no parent with type 1 diabetes was not disclosed. Moreover, the race and ethnicity of the study populations were not disclosed. 

DISCLOSURES:

The Wellcome Trust supported this study. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Young and adult children of mothers with type 1 diabetes are almost half as likely be diagnosed with this condition compared with those with affected fathers, even with a similar genetic risk score. 

METHODOLOGY:

• Individuals with a family history of type 1 diabetes face 8-15 times higher risk for this condition than the general population, with the risk of inheritance from mothers with type 1 diabetes being about half that of fathers with type 1 diabetes; however, it is unclear if the effect continues past childhood and what is responsible for the difference in risk.
• Researchers performed a meta-analysis across five cohort studies involving 11,475 individuals diagnosed with type 1 diabetes aged 0-88 years to evaluate if maternal type 1 diabetes conferred relative protection only to young children.
• They compared the proportion of individuals with type 1 diabetes with affected fathers versus mothers and explored if this comparison was altered by the age at diagnosis and the timing of parental diagnosis relative to the birth of the offspring.
• Lastly, the inherited genetic risk for type 1 diabetes was compared between those with affected mothers versus fathers using a risk score composed of more than 60 different gene variants associated with type 1 diabetes.

TAKEAWAY:

• Individuals with type 1 diabetes were almost twice as likely to have a father with the condition than a mother (odds ratio, 1.79; P < .0001).
• The protective effect of maternal diabetes was seen regardless of whether the individuals were diagnosed with type 1 diabetes before or after age 18 years (P < .0001).
• Maternal diabetes was linked to a lower risk for type 1 diabetes in children only if the mother had type 1 diabetes during pregnancy.
• The genetic risk score for type 1 diabetes was not significantly different between those with affected fathers versus mothers (P = .31).