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Topical retinoid plus benzoyl peroxide beats antibiotics for inflammatory acne
, according to the consensus of an international panel of dermatologists, led by Diane M. Thiboutot, MD, professor of dermatology, Penn State University, Hershey.
Dr. Thiboutot is the chair of the Global Alliance to Improve Outcomes in Acne, an international group of dermatologists interested in acne research and education; they have been meeting regularly since 2001 and continuously evaluate the literature on acne.
A Delphi panel and questionnaire method was used to reach consensus. A panel of 36 dermatologists from 27 countries who were members of the alliance answered a set of questionnaires on selected topics. An online questionnaire on various topics was developed, and panel members were asked to rate agreement with each statement on a 5-point Likert scale. If they selected disagree, strongly disagree, or unable to answer, they were asked to provide a written explanation of what they disagreed with. Ultimately, consensus was reached if 75% of more of the panel members agreed on a statement.
Assessing acne severity
The term “severe acne” currently is perceived to refer to nodular/conglobate acne, which is generally treated with oral isotretinoin. But development of added first-line treatment options means there may be a need for a system of classifying moderately severe, severe, and very severe acne. The 2016 European S3 Acne Guideline uses a 4-point classification system that might help: 1) comedonal acne, 2) mild-moderate papulopustular acne; 3) severe papulopustular acne, moderate nodular acne; and 4) severe nodular acne, conglobate acne. In a similar fashion, the U.S. Food and Drug Administration’s Investigator’s Global Assessment scale considers quality of lesions and quantity, including a grade of severe acne that is separate from nodular/conglobate acne.
“We propose that the designation “very severe” be reserved for cystic and conglobate acne,” Dr. Thiboutot and her associates wrote.
Strategic approach to acne therapy
First-line therapy for most patients with inflammatory acne, comedonal acne, or both, should be a topical retinoid plus topical benzoyl peroxide (BPO), the panelists agreed.
Topical or systemic antibiotics should not be used as monotherapy because of the rapid development of resistance. All strains of Propionibacterium acnes are sensitive to BPhO.
Topical retinoids (with or without BPO) or azelaic acid are the treatment of choice for maintenance, not topical antibiotics, they said.
Oral isotretinoin is indicated as first-line therapy for very severe (cystic and conglobate) acne. A small percentage of patients, perhaps 15%, experience acne flare on oral isotretinoin. This often can be managed by using low-dose therapy, say 0.5 mg/kg, although some panelists said that in some cases inflammatory flare occurs regardless of dose.
Oral tretinoin therapy should continue until full clearance of acne. More studies are needed to define the total cumulative dose that maintains remission, the alliance members said.
Determining the risk-benefit for using systemic antibiotics needs to balance individual need against public interest in preserving antibiotic effectiveness, the authors said. Antibiotics should be avoided when there are effective alternatives.
Oral antibiotics are indicated if inflammatory acne isn’t responding well to topical treatments, and acne involves the trunk or multiple bodily areas. Evaluate response to therapy at 6-8 weeks, and don’t treat for more than 3-4 months. After stopping antibiotics, use a topical retinoid and BPO or azelaic acid, they said.
The article, published in the Journal of the American Academy of Dermatology, provides an acne management algorithm that summarizes a treatment approach on the basis of these consensus recommendations.
Special populations
The panelists largely agreed that azelaic acid cream 20% or gel 15% can be useful to treat acne in pregnant women and patients with acne and postinflammatory hyperpigmention, although some said it can cause irritation and aggravate already inflamed skin.
In patients with inflammatory acne, devices such as laser, intense pulsed light, and photodynamic therapy should not be considered first-line treatment, they concluded.
The article also includes clinical pearls for treating acne and postinflammatory hyperpigmentation, questions to ask when taking an acne scar history, an atrophic acne scar risk-assessment tool, clinical pearls for preventing atrophic acne scars, interventions for treating facial atrophic acne scars, clinical pearls for preventing and managing hypertrophic or keloidal scars, and clinical pearls regarding acne in women.
The study is supported by an unrestricted educational grant from Galderma International SAS, Paris. All authors have served as advisory board members for Galderma and received honoraria. Dr. Thiboutot has received fees and research funding for serving as a consultant and investigator for Allergan, Mimetica, Novan, and Sebacia and as a consultant for Dermira, Galderma, Photosonix, and Xenon. Many of the other alliance members have financial associations with biopharmaceutical companies.
SOURCE: Thiboutot DM et al. J Am Acad Dermatol. 2018 Feb. doi: 10.1016/j.jaad.2017.09.078.
, according to the consensus of an international panel of dermatologists, led by Diane M. Thiboutot, MD, professor of dermatology, Penn State University, Hershey.
Dr. Thiboutot is the chair of the Global Alliance to Improve Outcomes in Acne, an international group of dermatologists interested in acne research and education; they have been meeting regularly since 2001 and continuously evaluate the literature on acne.
A Delphi panel and questionnaire method was used to reach consensus. A panel of 36 dermatologists from 27 countries who were members of the alliance answered a set of questionnaires on selected topics. An online questionnaire on various topics was developed, and panel members were asked to rate agreement with each statement on a 5-point Likert scale. If they selected disagree, strongly disagree, or unable to answer, they were asked to provide a written explanation of what they disagreed with. Ultimately, consensus was reached if 75% of more of the panel members agreed on a statement.
Assessing acne severity
The term “severe acne” currently is perceived to refer to nodular/conglobate acne, which is generally treated with oral isotretinoin. But development of added first-line treatment options means there may be a need for a system of classifying moderately severe, severe, and very severe acne. The 2016 European S3 Acne Guideline uses a 4-point classification system that might help: 1) comedonal acne, 2) mild-moderate papulopustular acne; 3) severe papulopustular acne, moderate nodular acne; and 4) severe nodular acne, conglobate acne. In a similar fashion, the U.S. Food and Drug Administration’s Investigator’s Global Assessment scale considers quality of lesions and quantity, including a grade of severe acne that is separate from nodular/conglobate acne.
“We propose that the designation “very severe” be reserved for cystic and conglobate acne,” Dr. Thiboutot and her associates wrote.
Strategic approach to acne therapy
First-line therapy for most patients with inflammatory acne, comedonal acne, or both, should be a topical retinoid plus topical benzoyl peroxide (BPO), the panelists agreed.
Topical or systemic antibiotics should not be used as monotherapy because of the rapid development of resistance. All strains of Propionibacterium acnes are sensitive to BPhO.
Topical retinoids (with or without BPO) or azelaic acid are the treatment of choice for maintenance, not topical antibiotics, they said.
Oral isotretinoin is indicated as first-line therapy for very severe (cystic and conglobate) acne. A small percentage of patients, perhaps 15%, experience acne flare on oral isotretinoin. This often can be managed by using low-dose therapy, say 0.5 mg/kg, although some panelists said that in some cases inflammatory flare occurs regardless of dose.
Oral tretinoin therapy should continue until full clearance of acne. More studies are needed to define the total cumulative dose that maintains remission, the alliance members said.
Determining the risk-benefit for using systemic antibiotics needs to balance individual need against public interest in preserving antibiotic effectiveness, the authors said. Antibiotics should be avoided when there are effective alternatives.
Oral antibiotics are indicated if inflammatory acne isn’t responding well to topical treatments, and acne involves the trunk or multiple bodily areas. Evaluate response to therapy at 6-8 weeks, and don’t treat for more than 3-4 months. After stopping antibiotics, use a topical retinoid and BPO or azelaic acid, they said.
The article, published in the Journal of the American Academy of Dermatology, provides an acne management algorithm that summarizes a treatment approach on the basis of these consensus recommendations.
Special populations
The panelists largely agreed that azelaic acid cream 20% or gel 15% can be useful to treat acne in pregnant women and patients with acne and postinflammatory hyperpigmention, although some said it can cause irritation and aggravate already inflamed skin.
In patients with inflammatory acne, devices such as laser, intense pulsed light, and photodynamic therapy should not be considered first-line treatment, they concluded.
The article also includes clinical pearls for treating acne and postinflammatory hyperpigmentation, questions to ask when taking an acne scar history, an atrophic acne scar risk-assessment tool, clinical pearls for preventing atrophic acne scars, interventions for treating facial atrophic acne scars, clinical pearls for preventing and managing hypertrophic or keloidal scars, and clinical pearls regarding acne in women.
The study is supported by an unrestricted educational grant from Galderma International SAS, Paris. All authors have served as advisory board members for Galderma and received honoraria. Dr. Thiboutot has received fees and research funding for serving as a consultant and investigator for Allergan, Mimetica, Novan, and Sebacia and as a consultant for Dermira, Galderma, Photosonix, and Xenon. Many of the other alliance members have financial associations with biopharmaceutical companies.
SOURCE: Thiboutot DM et al. J Am Acad Dermatol. 2018 Feb. doi: 10.1016/j.jaad.2017.09.078.
, according to the consensus of an international panel of dermatologists, led by Diane M. Thiboutot, MD, professor of dermatology, Penn State University, Hershey.
Dr. Thiboutot is the chair of the Global Alliance to Improve Outcomes in Acne, an international group of dermatologists interested in acne research and education; they have been meeting regularly since 2001 and continuously evaluate the literature on acne.
A Delphi panel and questionnaire method was used to reach consensus. A panel of 36 dermatologists from 27 countries who were members of the alliance answered a set of questionnaires on selected topics. An online questionnaire on various topics was developed, and panel members were asked to rate agreement with each statement on a 5-point Likert scale. If they selected disagree, strongly disagree, or unable to answer, they were asked to provide a written explanation of what they disagreed with. Ultimately, consensus was reached if 75% of more of the panel members agreed on a statement.
Assessing acne severity
The term “severe acne” currently is perceived to refer to nodular/conglobate acne, which is generally treated with oral isotretinoin. But development of added first-line treatment options means there may be a need for a system of classifying moderately severe, severe, and very severe acne. The 2016 European S3 Acne Guideline uses a 4-point classification system that might help: 1) comedonal acne, 2) mild-moderate papulopustular acne; 3) severe papulopustular acne, moderate nodular acne; and 4) severe nodular acne, conglobate acne. In a similar fashion, the U.S. Food and Drug Administration’s Investigator’s Global Assessment scale considers quality of lesions and quantity, including a grade of severe acne that is separate from nodular/conglobate acne.
“We propose that the designation “very severe” be reserved for cystic and conglobate acne,” Dr. Thiboutot and her associates wrote.
Strategic approach to acne therapy
First-line therapy for most patients with inflammatory acne, comedonal acne, or both, should be a topical retinoid plus topical benzoyl peroxide (BPO), the panelists agreed.
Topical or systemic antibiotics should not be used as monotherapy because of the rapid development of resistance. All strains of Propionibacterium acnes are sensitive to BPhO.
Topical retinoids (with or without BPO) or azelaic acid are the treatment of choice for maintenance, not topical antibiotics, they said.
Oral isotretinoin is indicated as first-line therapy for very severe (cystic and conglobate) acne. A small percentage of patients, perhaps 15%, experience acne flare on oral isotretinoin. This often can be managed by using low-dose therapy, say 0.5 mg/kg, although some panelists said that in some cases inflammatory flare occurs regardless of dose.
Oral tretinoin therapy should continue until full clearance of acne. More studies are needed to define the total cumulative dose that maintains remission, the alliance members said.
Determining the risk-benefit for using systemic antibiotics needs to balance individual need against public interest in preserving antibiotic effectiveness, the authors said. Antibiotics should be avoided when there are effective alternatives.
Oral antibiotics are indicated if inflammatory acne isn’t responding well to topical treatments, and acne involves the trunk or multiple bodily areas. Evaluate response to therapy at 6-8 weeks, and don’t treat for more than 3-4 months. After stopping antibiotics, use a topical retinoid and BPO or azelaic acid, they said.
The article, published in the Journal of the American Academy of Dermatology, provides an acne management algorithm that summarizes a treatment approach on the basis of these consensus recommendations.
Special populations
The panelists largely agreed that azelaic acid cream 20% or gel 15% can be useful to treat acne in pregnant women and patients with acne and postinflammatory hyperpigmention, although some said it can cause irritation and aggravate already inflamed skin.
In patients with inflammatory acne, devices such as laser, intense pulsed light, and photodynamic therapy should not be considered first-line treatment, they concluded.
The article also includes clinical pearls for treating acne and postinflammatory hyperpigmentation, questions to ask when taking an acne scar history, an atrophic acne scar risk-assessment tool, clinical pearls for preventing atrophic acne scars, interventions for treating facial atrophic acne scars, clinical pearls for preventing and managing hypertrophic or keloidal scars, and clinical pearls regarding acne in women.
The study is supported by an unrestricted educational grant from Galderma International SAS, Paris. All authors have served as advisory board members for Galderma and received honoraria. Dr. Thiboutot has received fees and research funding for serving as a consultant and investigator for Allergan, Mimetica, Novan, and Sebacia and as a consultant for Dermira, Galderma, Photosonix, and Xenon. Many of the other alliance members have financial associations with biopharmaceutical companies.
SOURCE: Thiboutot DM et al. J Am Acad Dermatol. 2018 Feb. doi: 10.1016/j.jaad.2017.09.078.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Approach to the asymptomatic adnexal mass: When to operate, refer, or observe
Adnexal masses are common findings in women. While the decision to operate on symptomatic adnexal masses is straightforward, the decision-making process for asymptomatic masses is more complicated. Here we address how to approach an asymptomatic adnexal mass, including how to decide when to operate, when to refer, or how to monitor.
It is important to minimize the number of surgeries for benign, asymptomatic adnexal masses because complications are reported in 2%-15% of surgeries for adnexal masses and these can range from minimal to devastating.1 In addition, unnecessary surgery is associated with a burden of cost to the health care system. Therefore, there is a paradigm shift in the management of asymptomatic adnexal masses trending toward surveillance of any masses that are likely to be benign. What becomes critical in this approach is the ability to accurately classify these masses preoperatively.
Determining the malignant potential of a mass
Guidance is provided by the ACOG Practice Bulletin Number 174, which was published in 2016: “Evaluation and Management of Adnexal Masses.”2 These guidelines remind clinicians that:
- Most adnexal masses are benign, even in postmenopausal patients.
- The recommended imaging modality is quality transvaginal ultrasonography with an ultrasonographer accredited through the American Registry of Diagnostic Medical Sonographers.
- Simple cysts up to 10 cm can be monitored using repeat imaging every 6 months without surgical intervention, even in postmenopausal patients. In prospective studies, no cases of malignancy were diagnosed over 6 years of surveillance and most resolved. Those that persist are likely to be serous cystadenomas.
- Many benign lesions such as endometriomas and cystic teratomas have characteristic radiologic features. Surgery for these lesions is warranted for large size, symptoms, or growth in size.
- Ultrasound characteristics of malignant masses include:
1. Cyst size greater than 10 cm
2. Papillary or solid components
3. Septations
4. Internal blood flow on color Doppler.
An alternative approach that has been proposed is an ultrasound scoring system devised by International Ovarian Tumor Analysis Group. The scoring system uses 10 ultrasound findings that are characteristic of malignant and benign and is designed to characterize masses as either benign or malignant.3 This approach is able to correctly classify 77% of masses. The remaining masses with features that do not fit the “simple rules” are considered potentially malignant and should be referred to an oncology specialist for further decision making.
Decision to operate
After referral to gynecologic oncologists, surgery is not always inevitable, particularly for women with indeterminate masses. The gynecologic oncologist uses a decision-making process that factors in the underlying surgical risks for that patient with the likelihood of malignancy based on the features of the mass. The threshold to operate is higher in women with underlying major comorbidities, such as morbid obesity, complex prior surgical history, or cardiopulmonary disease. Healthier surgical candidates are more likely to be considered for a surgery, even if the suspicion for malignancy is lower. However, low surgical risk does not equate to no surgical risk. Therefore, even in apparently “good” surgical candidates, the suspicion for underlying malignancy needs to be reasonably high in order to justify the cost and risk of surgery in an asymptomatic patient. Sometimes it is patient anxiety and a desire to avoid repeated surveillance that prompts a decision to operate.
How to monitor
The role of surveillance and monitoring is to establish a natural history of the lesion or to allow it to reveal itself to be stable or regressive. Surveillance with serial sonography has shown that most asymptomatic adnexal masses with low risk features will resolve over time. Lack of resolution in the setting of stable findings is not a worrisome feature and is not suggestive of malignancy. The mere persistence of an otherwise benign-appearing lesion is not a reason to intervene with surgery.
Unfortunately, there is no clear guidance on the surveillance intervals. Some experts recommend an initial repeat scan in 3 months. If at that point the morphologic features and size are stable or decreasing, ultrasounds can be repeated at annual intervals for 5 years. In one study, masses that became malignant demonstrated growth by 7 months. Other experts recommend limiting the period of surveillance of cystic lesions to 1 year and lesions with solid components to 2 years.
Conclusions
Many asymptomatic adnexal masses discovered on imaging can be monitored with serial sonography. Lesions with more worrisome morphology that’s suggestive of malignancy should prompt referral to a gynecologic oncologist. Surgery on benign masses can be avoided. Outcome data is needed to advise the optimal timing intervals and the limit of follow-up serial ultrasonography. A caveat of this watch-and-see approach is having to allay the patient’s fears of the malignant potential of the mass. This requires conversations with the patient informing them that the stability of the mass will be shown over time and that surgery can be safely avoided.
References
1. Glanc P et al. J Ultrasound Med. 2017;36:849-63.
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins – Gynecology. Obstet Gynecol. 2016 Nov;128(5):e210-26.
3. Timmerman D et al. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90.
Dr. Jackson-Moore is an associate professor in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC. They reported having no relevant financial disclosures.
Adnexal masses are common findings in women. While the decision to operate on symptomatic adnexal masses is straightforward, the decision-making process for asymptomatic masses is more complicated. Here we address how to approach an asymptomatic adnexal mass, including how to decide when to operate, when to refer, or how to monitor.
It is important to minimize the number of surgeries for benign, asymptomatic adnexal masses because complications are reported in 2%-15% of surgeries for adnexal masses and these can range from minimal to devastating.1 In addition, unnecessary surgery is associated with a burden of cost to the health care system. Therefore, there is a paradigm shift in the management of asymptomatic adnexal masses trending toward surveillance of any masses that are likely to be benign. What becomes critical in this approach is the ability to accurately classify these masses preoperatively.
Determining the malignant potential of a mass
Guidance is provided by the ACOG Practice Bulletin Number 174, which was published in 2016: “Evaluation and Management of Adnexal Masses.”2 These guidelines remind clinicians that:
- Most adnexal masses are benign, even in postmenopausal patients.
- The recommended imaging modality is quality transvaginal ultrasonography with an ultrasonographer accredited through the American Registry of Diagnostic Medical Sonographers.
- Simple cysts up to 10 cm can be monitored using repeat imaging every 6 months without surgical intervention, even in postmenopausal patients. In prospective studies, no cases of malignancy were diagnosed over 6 years of surveillance and most resolved. Those that persist are likely to be serous cystadenomas.
- Many benign lesions such as endometriomas and cystic teratomas have characteristic radiologic features. Surgery for these lesions is warranted for large size, symptoms, or growth in size.
- Ultrasound characteristics of malignant masses include:
1. Cyst size greater than 10 cm
2. Papillary or solid components
3. Septations
4. Internal blood flow on color Doppler.
An alternative approach that has been proposed is an ultrasound scoring system devised by International Ovarian Tumor Analysis Group. The scoring system uses 10 ultrasound findings that are characteristic of malignant and benign and is designed to characterize masses as either benign or malignant.3 This approach is able to correctly classify 77% of masses. The remaining masses with features that do not fit the “simple rules” are considered potentially malignant and should be referred to an oncology specialist for further decision making.
Decision to operate
After referral to gynecologic oncologists, surgery is not always inevitable, particularly for women with indeterminate masses. The gynecologic oncologist uses a decision-making process that factors in the underlying surgical risks for that patient with the likelihood of malignancy based on the features of the mass. The threshold to operate is higher in women with underlying major comorbidities, such as morbid obesity, complex prior surgical history, or cardiopulmonary disease. Healthier surgical candidates are more likely to be considered for a surgery, even if the suspicion for malignancy is lower. However, low surgical risk does not equate to no surgical risk. Therefore, even in apparently “good” surgical candidates, the suspicion for underlying malignancy needs to be reasonably high in order to justify the cost and risk of surgery in an asymptomatic patient. Sometimes it is patient anxiety and a desire to avoid repeated surveillance that prompts a decision to operate.
How to monitor
The role of surveillance and monitoring is to establish a natural history of the lesion or to allow it to reveal itself to be stable or regressive. Surveillance with serial sonography has shown that most asymptomatic adnexal masses with low risk features will resolve over time. Lack of resolution in the setting of stable findings is not a worrisome feature and is not suggestive of malignancy. The mere persistence of an otherwise benign-appearing lesion is not a reason to intervene with surgery.
Unfortunately, there is no clear guidance on the surveillance intervals. Some experts recommend an initial repeat scan in 3 months. If at that point the morphologic features and size are stable or decreasing, ultrasounds can be repeated at annual intervals for 5 years. In one study, masses that became malignant demonstrated growth by 7 months. Other experts recommend limiting the period of surveillance of cystic lesions to 1 year and lesions with solid components to 2 years.
Conclusions
Many asymptomatic adnexal masses discovered on imaging can be monitored with serial sonography. Lesions with more worrisome morphology that’s suggestive of malignancy should prompt referral to a gynecologic oncologist. Surgery on benign masses can be avoided. Outcome data is needed to advise the optimal timing intervals and the limit of follow-up serial ultrasonography. A caveat of this watch-and-see approach is having to allay the patient’s fears of the malignant potential of the mass. This requires conversations with the patient informing them that the stability of the mass will be shown over time and that surgery can be safely avoided.
References
1. Glanc P et al. J Ultrasound Med. 2017;36:849-63.
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins – Gynecology. Obstet Gynecol. 2016 Nov;128(5):e210-26.
3. Timmerman D et al. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90.
Dr. Jackson-Moore is an associate professor in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC. They reported having no relevant financial disclosures.
Adnexal masses are common findings in women. While the decision to operate on symptomatic adnexal masses is straightforward, the decision-making process for asymptomatic masses is more complicated. Here we address how to approach an asymptomatic adnexal mass, including how to decide when to operate, when to refer, or how to monitor.
It is important to minimize the number of surgeries for benign, asymptomatic adnexal masses because complications are reported in 2%-15% of surgeries for adnexal masses and these can range from minimal to devastating.1 In addition, unnecessary surgery is associated with a burden of cost to the health care system. Therefore, there is a paradigm shift in the management of asymptomatic adnexal masses trending toward surveillance of any masses that are likely to be benign. What becomes critical in this approach is the ability to accurately classify these masses preoperatively.
Determining the malignant potential of a mass
Guidance is provided by the ACOG Practice Bulletin Number 174, which was published in 2016: “Evaluation and Management of Adnexal Masses.”2 These guidelines remind clinicians that:
- Most adnexal masses are benign, even in postmenopausal patients.
- The recommended imaging modality is quality transvaginal ultrasonography with an ultrasonographer accredited through the American Registry of Diagnostic Medical Sonographers.
- Simple cysts up to 10 cm can be monitored using repeat imaging every 6 months without surgical intervention, even in postmenopausal patients. In prospective studies, no cases of malignancy were diagnosed over 6 years of surveillance and most resolved. Those that persist are likely to be serous cystadenomas.
- Many benign lesions such as endometriomas and cystic teratomas have characteristic radiologic features. Surgery for these lesions is warranted for large size, symptoms, or growth in size.
- Ultrasound characteristics of malignant masses include:
1. Cyst size greater than 10 cm
2. Papillary or solid components
3. Septations
4. Internal blood flow on color Doppler.
An alternative approach that has been proposed is an ultrasound scoring system devised by International Ovarian Tumor Analysis Group. The scoring system uses 10 ultrasound findings that are characteristic of malignant and benign and is designed to characterize masses as either benign or malignant.3 This approach is able to correctly classify 77% of masses. The remaining masses with features that do not fit the “simple rules” are considered potentially malignant and should be referred to an oncology specialist for further decision making.
Decision to operate
After referral to gynecologic oncologists, surgery is not always inevitable, particularly for women with indeterminate masses. The gynecologic oncologist uses a decision-making process that factors in the underlying surgical risks for that patient with the likelihood of malignancy based on the features of the mass. The threshold to operate is higher in women with underlying major comorbidities, such as morbid obesity, complex prior surgical history, or cardiopulmonary disease. Healthier surgical candidates are more likely to be considered for a surgery, even if the suspicion for malignancy is lower. However, low surgical risk does not equate to no surgical risk. Therefore, even in apparently “good” surgical candidates, the suspicion for underlying malignancy needs to be reasonably high in order to justify the cost and risk of surgery in an asymptomatic patient. Sometimes it is patient anxiety and a desire to avoid repeated surveillance that prompts a decision to operate.
How to monitor
The role of surveillance and monitoring is to establish a natural history of the lesion or to allow it to reveal itself to be stable or regressive. Surveillance with serial sonography has shown that most asymptomatic adnexal masses with low risk features will resolve over time. Lack of resolution in the setting of stable findings is not a worrisome feature and is not suggestive of malignancy. The mere persistence of an otherwise benign-appearing lesion is not a reason to intervene with surgery.
Unfortunately, there is no clear guidance on the surveillance intervals. Some experts recommend an initial repeat scan in 3 months. If at that point the morphologic features and size are stable or decreasing, ultrasounds can be repeated at annual intervals for 5 years. In one study, masses that became malignant demonstrated growth by 7 months. Other experts recommend limiting the period of surveillance of cystic lesions to 1 year and lesions with solid components to 2 years.
Conclusions
Many asymptomatic adnexal masses discovered on imaging can be monitored with serial sonography. Lesions with more worrisome morphology that’s suggestive of malignancy should prompt referral to a gynecologic oncologist. Surgery on benign masses can be avoided. Outcome data is needed to advise the optimal timing intervals and the limit of follow-up serial ultrasonography. A caveat of this watch-and-see approach is having to allay the patient’s fears of the malignant potential of the mass. This requires conversations with the patient informing them that the stability of the mass will be shown over time and that surgery can be safely avoided.
References
1. Glanc P et al. J Ultrasound Med. 2017;36:849-63.
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins – Gynecology. Obstet Gynecol. 2016 Nov;128(5):e210-26.
3. Timmerman D et al. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90.
Dr. Jackson-Moore is an associate professor in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC. They reported having no relevant financial disclosures.
Charting a new course in sepsis management
A drug overdose victim is admitted to a hospital. Providers focus on treating the overdose and blame it for some of the patient’s troubling vital signs, including low blood pressure and increased heart rate. Prior to admission, however, the patient had vomited and aspirated, leading to an infection. In fact, the patient is developing sepsis.
This real-world incident is but one of many ways that sepsis can fool hospitalists and other providers, often with rapidly deteriorating and deadly consequences. A range of quality improvement (QI) projects, however, are demonstrating how earlier identification and treatment may help to set a new course for addressing a condition that has remained stubbornly difficult to manage.
Devin J. Horton, MD, an academic hospitalist at University Hospital in Salt Lake City, sometimes compares sepsis to acute MI to illustrate the difficulty of early detection. A patient complaining of chest pain immediately sets in motion a well-rehearsed chain of events. “But the patient doesn’t look at you and say, ‘You know, I think I’m having SIRS [systemic inflammatory response syndrome] criteria in the setting of infection,’ ” he said. “And yet, the mortality of severe septic shock is at least as bad as acute myocardial infarction.” The trick is generating the same sense of urgency without a clear warning.
The location in a hospital also can present a major obstacle for early identification. Hospitalist Andy Odden, MD, SFHM, patient safety officer in the department of medicine at Washington University in St. Louis, calls hospital wards the “third space” of sepsis care, after the ICU and ED. “A lot of the historical improvement efforts and research has really focused on streamlining care in the ICU and streamlining care in the emergency department,” he said. Often, however, sepsis or septic shock isn’t recognized until a patient is admitted to a medical or surgical ward.
Observational studies by the Surviving Sepsis Campaign suggested that patients diagnosed on the floor had mortality rates comparable to and substantially higher than theoretically sicker patients diagnosed in the ICU and ED, respectively.1 “That was kind of a sea change for a lot of people and really articulated what a lot of us on the wards had been feeling,” Dr. Odden said. “We can’t simply apply the lessons that we’ve learned from the emergency department and the ICU to the wards if we’re going to provide the right care for these patients,” he said.
Dueling definitions
Better sepsis care in hospital wards will require a better understanding of shifting management guidelines. Confusing and contradictory definitions haven’t helped. In October 2015, the Centers for Medicare & Medicaid Services instituted its Sepsis Core Measure (SEP-1) for Medicare, requiring every hospital to audit a percentage of patients treated with best-practice 3- and 6-hour bundles for severe sepsis and septic shock. The SEP-1 measure uses the traditional definition of severe sepsis as two or more SIRS criteria, a suspected or proven infection, and organ dysfunction.
A separate set of guidelines issued by the international Sepsis-3 task force in February 2016, by contrast, concluded that the term “severe sepsis” is redundant.2 The update defines sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection” and asserts that the condition can be represented by an increase in the SOFA (Sequential Organ Failure Assessment) score of 2 or more points.
For hospital wards, the task force recommended a bedside scoring system called qSOFA (quickSOFA) for adult patients with a suspected infection. The risk stratification tool may help rapidly identify those who are likely to have poorer outcomes typical of sepsis if they meet two of the following three clinical criteria: a “respiratory rate of 22 [breaths]/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.”
CMS doesn’t recognize the Sepsis-3 definition at all and multiple providers have described widespread skepticism and uncertainty over how to reconcile it with the prior definition. Dr. Odden says the dueling definitions have “caused a tremendous amount of confusion” over diagnoses, the necessary sense of urgency, and whether severe sepsis is still a recognized entity. “When people aren’t speaking the same language with the same terminology, there is enormous opportunity for miscommunication to occur,” he said.
Obtaining reliable scores is another matter. The qSOFA blood pressure score generally is measured accurately, he said. On noncritical care units, though, nurses aren’t always trained to consistently and accurately document a patient’s mental status. Likewise, he said, documentation of respiratory rate often is subjective, and an abnormal rate can be easily missed. Changing that dynamic, he stressed, will require coordination with nursing leadership to ensure more consistent and accurate measurements.
Reshaping sepsis pathways
So how can hospitals identify sepsis sooner? Some hospitals have relied more on EMR-based screening methods; others have relied more on nurses to lead the charge. Either way, Dr. Shieh said, the field is trying to encourage the use of set pathways. Almost every medical center that performs well on sepsis measures, she says, has a good screening program, a pathway implemented through an order set or nursing staff, and a highly trained sepsis team that ensures patients get the treatment they need.
At Middlesex Hospital in Middletown, Conn., a major QI project led to significant improvements in sepsis mortality, total mortality, sepsis-related serious safety events and sepsis length of stay. Terri Savino, MSN, RN, CPHQ, the hospital’s manager of patient experience and service excellence, said the project sprang from concerns by the hospital’s Rapid Response Review Committee about some serious safety events involving a delay in sepsis diagnosis and treatment.
In 2013, the hospital documented three serious safety events related to a delay in diagnosis and treatment of sepsis. In 2014, it recorded only one event and has had none since then. From 2014 to 2015, sepsis-related mortality fell by more than 20%, saving an estimated 25 lives. Sepsis length of stay also declined. “We’re identifying them sooner and treating them sooner so they’re not getting as sick or requiring critical care and longer length of stays,” Ms. Savino said.
Dr. Odden has participated in two multicenter QI initiatives on sepsis. One, a partnership led by the Institute for Healthcare Improvement in Cambridge, Mass., and New York’s North Shore-LIJ Health System, focused on how to diagnose sepsis in hospital ward patients as quickly as possible and how to successfully deliver the 3-hour sepsis bundle.3 Beyond getting everyone on the same page regarding definitions, he said, the collaborators discussed and shared strategies for identifying patients. “One hospital would often have a solution for a problem that other hospitals could either take directly or modify based on their own understanding of their own processes,” he said.
Dr. Odden also participated in a national project sponsored by the Surviving Sepsis Campaign that focused on developing protocols for nurse-led screening processes in hospital wards. Within a pilot unit of each participating hospital, bedside nurses screened every patient for sepsis during every shift. For positive screens, the hospitals then developed protocols for order sets, like blood work and fluids.
The initiative suggested that a nurse-based, every-shift screening method might be one feasible way to identify sick patients as early as possible. “Going through the screening process really seemed to empower the nurses to take a much more active role in partnering with the physicians and in recognizing some of the early warning signs,” Dr. Odden said. The project led to other benefits as well, including improved identification of strokes, delirium, and even a gastrointestinal bleed because the “barriers in communication had been broken down,” he said.
To help medical providers recognize sepsis earlier, Dr. Shieh and her colleagues created a free game called Septris as an adjunctive teaching tool. Based on a player’s diagnosis and treatment decisions, patient outcomes either rise or fall – often rapidly. “I’m an educator and what I know is that the best way you learn is by doing,” she said. The interactive and repetitive nature of Septris, she said, helps its take-home messages stick in a player’s mind without the expense of patient simulations. Dr. Shieh said the game has been adapted for German and British medical institutions as well, and that she collects data from players around the world about their experiences and scores.
Winning interdisciplinary buy-in
To maximize the chances for success, several doctors emphasize the importance of forming an interdisciplinary task force that includes every department affected by a QI project. Ms. Savino said executive sponsorship of her hospital’s QI project was key as well. So was meeting frequently with the carefully chosen team members representing key stakeholders throughout the hospital. “It was a lot of work,” she said. “But I really think that was one reason why it was so successful. We had everybody’s buy-in, and we kept our short-term goals on track.”
Based on their success, the QI initiative has spread to two other hospitals in the University of Utah’s network. “Once the culture changes have been made and the project’s up and going, it’s kind of self-sufficient,” Dr. Horton said. “But it was so much work.” He and Dr. Graves are careful to emphasize that there are other options for sepsis-related QI efforts. “I think it is better to start something small than to believe you can’t do anything at all,” Dr. Graves said.
No matter what the size, assembling a motivated and multidisciplinary team is critical, she said. So is empowering nurses to talk to physicians about decompensating patients and other aspects of sepsis care. Being available and willing to listen to other providers also can pay big dividends. “Knowing that we cared about the project’s success was important to people working on it,” Dr. Graves said.
Despite the remaining challenges, Dr. Shieh points out that sepsis mortality rates have improved significantly, thanks in large part to more awareness and ambitious QI projects. “I do want to say that we have come a long way,” she said.
References
1. Levy MM et al. Surviving Sepsis Campaign: Association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med. 2014 Nov;40(11):1623-33.
2. Singer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-10.
3. Schorr C et al. Implementation of a multicenter performance improvement program for early detection and treatment of severe sepsis in general medical-surgical wards. J Hosp Med. 2016 Nov;11:S32-9.
4. Lee VS et al. Implementation of a value-driven outcomes program to identify high variability in clinical costs and outcomes and association with reduced cost and improved quality. JAMA. 2016 Sep 13;316(10):1061-72.
A drug overdose victim is admitted to a hospital. Providers focus on treating the overdose and blame it for some of the patient’s troubling vital signs, including low blood pressure and increased heart rate. Prior to admission, however, the patient had vomited and aspirated, leading to an infection. In fact, the patient is developing sepsis.
This real-world incident is but one of many ways that sepsis can fool hospitalists and other providers, often with rapidly deteriorating and deadly consequences. A range of quality improvement (QI) projects, however, are demonstrating how earlier identification and treatment may help to set a new course for addressing a condition that has remained stubbornly difficult to manage.
Devin J. Horton, MD, an academic hospitalist at University Hospital in Salt Lake City, sometimes compares sepsis to acute MI to illustrate the difficulty of early detection. A patient complaining of chest pain immediately sets in motion a well-rehearsed chain of events. “But the patient doesn’t look at you and say, ‘You know, I think I’m having SIRS [systemic inflammatory response syndrome] criteria in the setting of infection,’ ” he said. “And yet, the mortality of severe septic shock is at least as bad as acute myocardial infarction.” The trick is generating the same sense of urgency without a clear warning.
The location in a hospital also can present a major obstacle for early identification. Hospitalist Andy Odden, MD, SFHM, patient safety officer in the department of medicine at Washington University in St. Louis, calls hospital wards the “third space” of sepsis care, after the ICU and ED. “A lot of the historical improvement efforts and research has really focused on streamlining care in the ICU and streamlining care in the emergency department,” he said. Often, however, sepsis or septic shock isn’t recognized until a patient is admitted to a medical or surgical ward.
Observational studies by the Surviving Sepsis Campaign suggested that patients diagnosed on the floor had mortality rates comparable to and substantially higher than theoretically sicker patients diagnosed in the ICU and ED, respectively.1 “That was kind of a sea change for a lot of people and really articulated what a lot of us on the wards had been feeling,” Dr. Odden said. “We can’t simply apply the lessons that we’ve learned from the emergency department and the ICU to the wards if we’re going to provide the right care for these patients,” he said.
Dueling definitions
Better sepsis care in hospital wards will require a better understanding of shifting management guidelines. Confusing and contradictory definitions haven’t helped. In October 2015, the Centers for Medicare & Medicaid Services instituted its Sepsis Core Measure (SEP-1) for Medicare, requiring every hospital to audit a percentage of patients treated with best-practice 3- and 6-hour bundles for severe sepsis and septic shock. The SEP-1 measure uses the traditional definition of severe sepsis as two or more SIRS criteria, a suspected or proven infection, and organ dysfunction.
A separate set of guidelines issued by the international Sepsis-3 task force in February 2016, by contrast, concluded that the term “severe sepsis” is redundant.2 The update defines sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection” and asserts that the condition can be represented by an increase in the SOFA (Sequential Organ Failure Assessment) score of 2 or more points.
For hospital wards, the task force recommended a bedside scoring system called qSOFA (quickSOFA) for adult patients with a suspected infection. The risk stratification tool may help rapidly identify those who are likely to have poorer outcomes typical of sepsis if they meet two of the following three clinical criteria: a “respiratory rate of 22 [breaths]/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.”
CMS doesn’t recognize the Sepsis-3 definition at all and multiple providers have described widespread skepticism and uncertainty over how to reconcile it with the prior definition. Dr. Odden says the dueling definitions have “caused a tremendous amount of confusion” over diagnoses, the necessary sense of urgency, and whether severe sepsis is still a recognized entity. “When people aren’t speaking the same language with the same terminology, there is enormous opportunity for miscommunication to occur,” he said.
Obtaining reliable scores is another matter. The qSOFA blood pressure score generally is measured accurately, he said. On noncritical care units, though, nurses aren’t always trained to consistently and accurately document a patient’s mental status. Likewise, he said, documentation of respiratory rate often is subjective, and an abnormal rate can be easily missed. Changing that dynamic, he stressed, will require coordination with nursing leadership to ensure more consistent and accurate measurements.
Reshaping sepsis pathways
So how can hospitals identify sepsis sooner? Some hospitals have relied more on EMR-based screening methods; others have relied more on nurses to lead the charge. Either way, Dr. Shieh said, the field is trying to encourage the use of set pathways. Almost every medical center that performs well on sepsis measures, she says, has a good screening program, a pathway implemented through an order set or nursing staff, and a highly trained sepsis team that ensures patients get the treatment they need.
At Middlesex Hospital in Middletown, Conn., a major QI project led to significant improvements in sepsis mortality, total mortality, sepsis-related serious safety events and sepsis length of stay. Terri Savino, MSN, RN, CPHQ, the hospital’s manager of patient experience and service excellence, said the project sprang from concerns by the hospital’s Rapid Response Review Committee about some serious safety events involving a delay in sepsis diagnosis and treatment.
In 2013, the hospital documented three serious safety events related to a delay in diagnosis and treatment of sepsis. In 2014, it recorded only one event and has had none since then. From 2014 to 2015, sepsis-related mortality fell by more than 20%, saving an estimated 25 lives. Sepsis length of stay also declined. “We’re identifying them sooner and treating them sooner so they’re not getting as sick or requiring critical care and longer length of stays,” Ms. Savino said.
Dr. Odden has participated in two multicenter QI initiatives on sepsis. One, a partnership led by the Institute for Healthcare Improvement in Cambridge, Mass., and New York’s North Shore-LIJ Health System, focused on how to diagnose sepsis in hospital ward patients as quickly as possible and how to successfully deliver the 3-hour sepsis bundle.3 Beyond getting everyone on the same page regarding definitions, he said, the collaborators discussed and shared strategies for identifying patients. “One hospital would often have a solution for a problem that other hospitals could either take directly or modify based on their own understanding of their own processes,” he said.
Dr. Odden also participated in a national project sponsored by the Surviving Sepsis Campaign that focused on developing protocols for nurse-led screening processes in hospital wards. Within a pilot unit of each participating hospital, bedside nurses screened every patient for sepsis during every shift. For positive screens, the hospitals then developed protocols for order sets, like blood work and fluids.
The initiative suggested that a nurse-based, every-shift screening method might be one feasible way to identify sick patients as early as possible. “Going through the screening process really seemed to empower the nurses to take a much more active role in partnering with the physicians and in recognizing some of the early warning signs,” Dr. Odden said. The project led to other benefits as well, including improved identification of strokes, delirium, and even a gastrointestinal bleed because the “barriers in communication had been broken down,” he said.
To help medical providers recognize sepsis earlier, Dr. Shieh and her colleagues created a free game called Septris as an adjunctive teaching tool. Based on a player’s diagnosis and treatment decisions, patient outcomes either rise or fall – often rapidly. “I’m an educator and what I know is that the best way you learn is by doing,” she said. The interactive and repetitive nature of Septris, she said, helps its take-home messages stick in a player’s mind without the expense of patient simulations. Dr. Shieh said the game has been adapted for German and British medical institutions as well, and that she collects data from players around the world about their experiences and scores.
Winning interdisciplinary buy-in
To maximize the chances for success, several doctors emphasize the importance of forming an interdisciplinary task force that includes every department affected by a QI project. Ms. Savino said executive sponsorship of her hospital’s QI project was key as well. So was meeting frequently with the carefully chosen team members representing key stakeholders throughout the hospital. “It was a lot of work,” she said. “But I really think that was one reason why it was so successful. We had everybody’s buy-in, and we kept our short-term goals on track.”
Based on their success, the QI initiative has spread to two other hospitals in the University of Utah’s network. “Once the culture changes have been made and the project’s up and going, it’s kind of self-sufficient,” Dr. Horton said. “But it was so much work.” He and Dr. Graves are careful to emphasize that there are other options for sepsis-related QI efforts. “I think it is better to start something small than to believe you can’t do anything at all,” Dr. Graves said.
No matter what the size, assembling a motivated and multidisciplinary team is critical, she said. So is empowering nurses to talk to physicians about decompensating patients and other aspects of sepsis care. Being available and willing to listen to other providers also can pay big dividends. “Knowing that we cared about the project’s success was important to people working on it,” Dr. Graves said.
Despite the remaining challenges, Dr. Shieh points out that sepsis mortality rates have improved significantly, thanks in large part to more awareness and ambitious QI projects. “I do want to say that we have come a long way,” she said.
References
1. Levy MM et al. Surviving Sepsis Campaign: Association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med. 2014 Nov;40(11):1623-33.
2. Singer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-10.
3. Schorr C et al. Implementation of a multicenter performance improvement program for early detection and treatment of severe sepsis in general medical-surgical wards. J Hosp Med. 2016 Nov;11:S32-9.
4. Lee VS et al. Implementation of a value-driven outcomes program to identify high variability in clinical costs and outcomes and association with reduced cost and improved quality. JAMA. 2016 Sep 13;316(10):1061-72.
A drug overdose victim is admitted to a hospital. Providers focus on treating the overdose and blame it for some of the patient’s troubling vital signs, including low blood pressure and increased heart rate. Prior to admission, however, the patient had vomited and aspirated, leading to an infection. In fact, the patient is developing sepsis.
This real-world incident is but one of many ways that sepsis can fool hospitalists and other providers, often with rapidly deteriorating and deadly consequences. A range of quality improvement (QI) projects, however, are demonstrating how earlier identification and treatment may help to set a new course for addressing a condition that has remained stubbornly difficult to manage.
Devin J. Horton, MD, an academic hospitalist at University Hospital in Salt Lake City, sometimes compares sepsis to acute MI to illustrate the difficulty of early detection. A patient complaining of chest pain immediately sets in motion a well-rehearsed chain of events. “But the patient doesn’t look at you and say, ‘You know, I think I’m having SIRS [systemic inflammatory response syndrome] criteria in the setting of infection,’ ” he said. “And yet, the mortality of severe septic shock is at least as bad as acute myocardial infarction.” The trick is generating the same sense of urgency without a clear warning.
The location in a hospital also can present a major obstacle for early identification. Hospitalist Andy Odden, MD, SFHM, patient safety officer in the department of medicine at Washington University in St. Louis, calls hospital wards the “third space” of sepsis care, after the ICU and ED. “A lot of the historical improvement efforts and research has really focused on streamlining care in the ICU and streamlining care in the emergency department,” he said. Often, however, sepsis or septic shock isn’t recognized until a patient is admitted to a medical or surgical ward.
Observational studies by the Surviving Sepsis Campaign suggested that patients diagnosed on the floor had mortality rates comparable to and substantially higher than theoretically sicker patients diagnosed in the ICU and ED, respectively.1 “That was kind of a sea change for a lot of people and really articulated what a lot of us on the wards had been feeling,” Dr. Odden said. “We can’t simply apply the lessons that we’ve learned from the emergency department and the ICU to the wards if we’re going to provide the right care for these patients,” he said.
Dueling definitions
Better sepsis care in hospital wards will require a better understanding of shifting management guidelines. Confusing and contradictory definitions haven’t helped. In October 2015, the Centers for Medicare & Medicaid Services instituted its Sepsis Core Measure (SEP-1) for Medicare, requiring every hospital to audit a percentage of patients treated with best-practice 3- and 6-hour bundles for severe sepsis and septic shock. The SEP-1 measure uses the traditional definition of severe sepsis as two or more SIRS criteria, a suspected or proven infection, and organ dysfunction.
A separate set of guidelines issued by the international Sepsis-3 task force in February 2016, by contrast, concluded that the term “severe sepsis” is redundant.2 The update defines sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection” and asserts that the condition can be represented by an increase in the SOFA (Sequential Organ Failure Assessment) score of 2 or more points.
For hospital wards, the task force recommended a bedside scoring system called qSOFA (quickSOFA) for adult patients with a suspected infection. The risk stratification tool may help rapidly identify those who are likely to have poorer outcomes typical of sepsis if they meet two of the following three clinical criteria: a “respiratory rate of 22 [breaths]/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.”
CMS doesn’t recognize the Sepsis-3 definition at all and multiple providers have described widespread skepticism and uncertainty over how to reconcile it with the prior definition. Dr. Odden says the dueling definitions have “caused a tremendous amount of confusion” over diagnoses, the necessary sense of urgency, and whether severe sepsis is still a recognized entity. “When people aren’t speaking the same language with the same terminology, there is enormous opportunity for miscommunication to occur,” he said.
Obtaining reliable scores is another matter. The qSOFA blood pressure score generally is measured accurately, he said. On noncritical care units, though, nurses aren’t always trained to consistently and accurately document a patient’s mental status. Likewise, he said, documentation of respiratory rate often is subjective, and an abnormal rate can be easily missed. Changing that dynamic, he stressed, will require coordination with nursing leadership to ensure more consistent and accurate measurements.
Reshaping sepsis pathways
So how can hospitals identify sepsis sooner? Some hospitals have relied more on EMR-based screening methods; others have relied more on nurses to lead the charge. Either way, Dr. Shieh said, the field is trying to encourage the use of set pathways. Almost every medical center that performs well on sepsis measures, she says, has a good screening program, a pathway implemented through an order set or nursing staff, and a highly trained sepsis team that ensures patients get the treatment they need.
At Middlesex Hospital in Middletown, Conn., a major QI project led to significant improvements in sepsis mortality, total mortality, sepsis-related serious safety events and sepsis length of stay. Terri Savino, MSN, RN, CPHQ, the hospital’s manager of patient experience and service excellence, said the project sprang from concerns by the hospital’s Rapid Response Review Committee about some serious safety events involving a delay in sepsis diagnosis and treatment.
In 2013, the hospital documented three serious safety events related to a delay in diagnosis and treatment of sepsis. In 2014, it recorded only one event and has had none since then. From 2014 to 2015, sepsis-related mortality fell by more than 20%, saving an estimated 25 lives. Sepsis length of stay also declined. “We’re identifying them sooner and treating them sooner so they’re not getting as sick or requiring critical care and longer length of stays,” Ms. Savino said.
Dr. Odden has participated in two multicenter QI initiatives on sepsis. One, a partnership led by the Institute for Healthcare Improvement in Cambridge, Mass., and New York’s North Shore-LIJ Health System, focused on how to diagnose sepsis in hospital ward patients as quickly as possible and how to successfully deliver the 3-hour sepsis bundle.3 Beyond getting everyone on the same page regarding definitions, he said, the collaborators discussed and shared strategies for identifying patients. “One hospital would often have a solution for a problem that other hospitals could either take directly or modify based on their own understanding of their own processes,” he said.
Dr. Odden also participated in a national project sponsored by the Surviving Sepsis Campaign that focused on developing protocols for nurse-led screening processes in hospital wards. Within a pilot unit of each participating hospital, bedside nurses screened every patient for sepsis during every shift. For positive screens, the hospitals then developed protocols for order sets, like blood work and fluids.
The initiative suggested that a nurse-based, every-shift screening method might be one feasible way to identify sick patients as early as possible. “Going through the screening process really seemed to empower the nurses to take a much more active role in partnering with the physicians and in recognizing some of the early warning signs,” Dr. Odden said. The project led to other benefits as well, including improved identification of strokes, delirium, and even a gastrointestinal bleed because the “barriers in communication had been broken down,” he said.
To help medical providers recognize sepsis earlier, Dr. Shieh and her colleagues created a free game called Septris as an adjunctive teaching tool. Based on a player’s diagnosis and treatment decisions, patient outcomes either rise or fall – often rapidly. “I’m an educator and what I know is that the best way you learn is by doing,” she said. The interactive and repetitive nature of Septris, she said, helps its take-home messages stick in a player’s mind without the expense of patient simulations. Dr. Shieh said the game has been adapted for German and British medical institutions as well, and that she collects data from players around the world about their experiences and scores.
Winning interdisciplinary buy-in
To maximize the chances for success, several doctors emphasize the importance of forming an interdisciplinary task force that includes every department affected by a QI project. Ms. Savino said executive sponsorship of her hospital’s QI project was key as well. So was meeting frequently with the carefully chosen team members representing key stakeholders throughout the hospital. “It was a lot of work,” she said. “But I really think that was one reason why it was so successful. We had everybody’s buy-in, and we kept our short-term goals on track.”
Based on their success, the QI initiative has spread to two other hospitals in the University of Utah’s network. “Once the culture changes have been made and the project’s up and going, it’s kind of self-sufficient,” Dr. Horton said. “But it was so much work.” He and Dr. Graves are careful to emphasize that there are other options for sepsis-related QI efforts. “I think it is better to start something small than to believe you can’t do anything at all,” Dr. Graves said.
No matter what the size, assembling a motivated and multidisciplinary team is critical, she said. So is empowering nurses to talk to physicians about decompensating patients and other aspects of sepsis care. Being available and willing to listen to other providers also can pay big dividends. “Knowing that we cared about the project’s success was important to people working on it,” Dr. Graves said.
Despite the remaining challenges, Dr. Shieh points out that sepsis mortality rates have improved significantly, thanks in large part to more awareness and ambitious QI projects. “I do want to say that we have come a long way,” she said.
References
1. Levy MM et al. Surviving Sepsis Campaign: Association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med. 2014 Nov;40(11):1623-33.
2. Singer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-10.
3. Schorr C et al. Implementation of a multicenter performance improvement program for early detection and treatment of severe sepsis in general medical-surgical wards. J Hosp Med. 2016 Nov;11:S32-9.
4. Lee VS et al. Implementation of a value-driven outcomes program to identify high variability in clinical costs and outcomes and association with reduced cost and improved quality. JAMA. 2016 Sep 13;316(10):1061-72.
Novel JAK1 inhibitor shows promise for myeloid malignancies
ATLANTA – The novel Janus kinase 1 (JAK1) inhibitor INCB052793 showed encouraging activity, particularly in combination with azacitidine, in certain patients with advanced myeloid malignancies in a phase 1/2 trial.
The activity was seen even in patients who previously failed treatment with hypomethylating agents, Amer M. Zeidan, MD, reported at the annual meeting of the American Society of Hematology.
In the combination therapy dose escalation phase (phase 1b), seven patients with MM received INCB052793 at doses of 25 mg or 35 mg daily plus dexamethasone, and nine patients with acute myeloid leukemia (AML) or MDS received INCB052793 plus azacitidine. During the dose expansion, 12 patients received a daily dose of 35 mg for 28-day cycles plus azacitidine (in AML and MDS patients), according to Dr. Zeidan of Yale University, New Haven, Conn.
The study employed a 3+3 dose-escalation design until dose-limiting toxicities occurred. Patients were treated in continuous cycles until study termination, consent withdrawal, disease progression, or unacceptable toxicity.
Phase 2 of the study is evaluating INCB052793 in combination with azacitidine in nine patients with AML or high-risk MDS who failed prior therapy with hypomethylating agents. The 35-mg daily dose was selected for this phase based on pharmacodynamic effect and the presence of thrombocytopenia in solid tumor patients at higher doses, he said.
At the data cutoff for this preliminary assessment, 1 of the 11 patients who received INCB052793 monotherapy – a patient with MDS/MPN – experienced complete response (CR) and remained on study at the data cutoff. Two monotherapy patients with MDS/MPN experienced partial remission (PR).
Of seven patients with MM in the INCB052793-plus-dexamethasone group, two had a minimal response with a reduction in M protein.
In the INCB052793-plus-azacitidine group, overall response rates were 67% in 12 patients with AML and 56% in patients with MDS or MDS/MPN.
In the AML group, there was one CR, one morphologic leukemia-free state, and two PRs. In the MDS group, three of seven patients had a CR. Among the two patients in the MDS/MPN group, one had a CR and one had a PR.
Of note, none of the seven patients in the INCB052793-plus-dexamethasone group had received prior treatment with hypomethylating agents, while 10 of 21 patients in the INCB052793-plus-azacitidine phase 1b group had, as well as all of the nine phase 2 patients. The results were as of Nov. 3, 2017, Dr. Zeidan said.
The JAK/STAT pathway plays an important role in cytokine and growth factor signal transduction. Dysregulation of the JAK/STAT pathway is associated with the pathogenesis of various hematologic malignancies, Dr. Zeidan explained, noting that blocking JAK signaling can inhibit AML cell proliferation through STAT3/5 inhibition and induction of caspase-dependent apoptosis.
INCB052793 is a small molecule JAK1 inhibitor with potential as monotherapy or in combination with standard therapies for treating advanced hematologic malignancies. It could be of particular benefit for high-risk MDS patients who have failed prior therapy with hypomethylating agents, as these patients have no available standard of care and their overall survival is often less than 6 months, he said.
These preliminary data show that treatment is associated with a number of nonhematologic and hematologic adverse events. Grade 3 or greater adverse events were observed in 45% of patients receiving INCB052793 monotherapy, 86% of patients receiving INCB052793 plus dexamethasone, and 95% of those receiving INCB052793 plus azacitidine.
The most common adverse events with INCB052793 plus dexamethasone were anemia, hypercalcemia, hypophosphatemia, pneumonia, sepsis, and thrombocytopenia. With INCB052793 plus azacitidine, the most common events were febrile neutropenia, anemia, neutropenia, and thrombocytopenia.
Most patients included in the current analysis discontinued treatment, including 91% of INCB052793 monotherapy patients, 100% of INCB052793-plus-dexamethasone patients, and 90% of INCB052793-plus-azacitidine patients. The primary reasons for discontinuation were disease progression or adverse events.
Despite these events, the findings suggest that combination therapy with INCB052793 and azacitidine is promising for patients with advanced myeloid malignancies, Dr. Zeidan said. However, signals of activity were lacking in multiple myeloma or lymphoid malignancies.
The findings of encouraging activity in patients who previously failed on hypomethylating agents are of particular interest, and suggest that INCB052793 might resensitize refractory/relapsed patients to the effects of these agents, Dr. Zeidan noted, concluding that these preliminary safety and efficacy data support further evaluation of INCB052793 in this setting. Enrollment is ongoing in phase 2 of the trial.
This study is sponsored by Incyte. Dr. Zeidan reported serving as a consultant for Incyte and Otsuka and as a member of the speakers bureau for Takeda. He also reported financial relationships with AbbVie, Pfizer, Gilead, Celgene, and Ariad.
SOURCE: Zeidan A et al. ASH 2017 Abstract 640.
ATLANTA – The novel Janus kinase 1 (JAK1) inhibitor INCB052793 showed encouraging activity, particularly in combination with azacitidine, in certain patients with advanced myeloid malignancies in a phase 1/2 trial.
The activity was seen even in patients who previously failed treatment with hypomethylating agents, Amer M. Zeidan, MD, reported at the annual meeting of the American Society of Hematology.
In the combination therapy dose escalation phase (phase 1b), seven patients with MM received INCB052793 at doses of 25 mg or 35 mg daily plus dexamethasone, and nine patients with acute myeloid leukemia (AML) or MDS received INCB052793 plus azacitidine. During the dose expansion, 12 patients received a daily dose of 35 mg for 28-day cycles plus azacitidine (in AML and MDS patients), according to Dr. Zeidan of Yale University, New Haven, Conn.
The study employed a 3+3 dose-escalation design until dose-limiting toxicities occurred. Patients were treated in continuous cycles until study termination, consent withdrawal, disease progression, or unacceptable toxicity.
Phase 2 of the study is evaluating INCB052793 in combination with azacitidine in nine patients with AML or high-risk MDS who failed prior therapy with hypomethylating agents. The 35-mg daily dose was selected for this phase based on pharmacodynamic effect and the presence of thrombocytopenia in solid tumor patients at higher doses, he said.
At the data cutoff for this preliminary assessment, 1 of the 11 patients who received INCB052793 monotherapy – a patient with MDS/MPN – experienced complete response (CR) and remained on study at the data cutoff. Two monotherapy patients with MDS/MPN experienced partial remission (PR).
Of seven patients with MM in the INCB052793-plus-dexamethasone group, two had a minimal response with a reduction in M protein.
In the INCB052793-plus-azacitidine group, overall response rates were 67% in 12 patients with AML and 56% in patients with MDS or MDS/MPN.
In the AML group, there was one CR, one morphologic leukemia-free state, and two PRs. In the MDS group, three of seven patients had a CR. Among the two patients in the MDS/MPN group, one had a CR and one had a PR.
Of note, none of the seven patients in the INCB052793-plus-dexamethasone group had received prior treatment with hypomethylating agents, while 10 of 21 patients in the INCB052793-plus-azacitidine phase 1b group had, as well as all of the nine phase 2 patients. The results were as of Nov. 3, 2017, Dr. Zeidan said.
The JAK/STAT pathway plays an important role in cytokine and growth factor signal transduction. Dysregulation of the JAK/STAT pathway is associated with the pathogenesis of various hematologic malignancies, Dr. Zeidan explained, noting that blocking JAK signaling can inhibit AML cell proliferation through STAT3/5 inhibition and induction of caspase-dependent apoptosis.
INCB052793 is a small molecule JAK1 inhibitor with potential as monotherapy or in combination with standard therapies for treating advanced hematologic malignancies. It could be of particular benefit for high-risk MDS patients who have failed prior therapy with hypomethylating agents, as these patients have no available standard of care and their overall survival is often less than 6 months, he said.
These preliminary data show that treatment is associated with a number of nonhematologic and hematologic adverse events. Grade 3 or greater adverse events were observed in 45% of patients receiving INCB052793 monotherapy, 86% of patients receiving INCB052793 plus dexamethasone, and 95% of those receiving INCB052793 plus azacitidine.
The most common adverse events with INCB052793 plus dexamethasone were anemia, hypercalcemia, hypophosphatemia, pneumonia, sepsis, and thrombocytopenia. With INCB052793 plus azacitidine, the most common events were febrile neutropenia, anemia, neutropenia, and thrombocytopenia.
Most patients included in the current analysis discontinued treatment, including 91% of INCB052793 monotherapy patients, 100% of INCB052793-plus-dexamethasone patients, and 90% of INCB052793-plus-azacitidine patients. The primary reasons for discontinuation were disease progression or adverse events.
Despite these events, the findings suggest that combination therapy with INCB052793 and azacitidine is promising for patients with advanced myeloid malignancies, Dr. Zeidan said. However, signals of activity were lacking in multiple myeloma or lymphoid malignancies.
The findings of encouraging activity in patients who previously failed on hypomethylating agents are of particular interest, and suggest that INCB052793 might resensitize refractory/relapsed patients to the effects of these agents, Dr. Zeidan noted, concluding that these preliminary safety and efficacy data support further evaluation of INCB052793 in this setting. Enrollment is ongoing in phase 2 of the trial.
This study is sponsored by Incyte. Dr. Zeidan reported serving as a consultant for Incyte and Otsuka and as a member of the speakers bureau for Takeda. He also reported financial relationships with AbbVie, Pfizer, Gilead, Celgene, and Ariad.
SOURCE: Zeidan A et al. ASH 2017 Abstract 640.
ATLANTA – The novel Janus kinase 1 (JAK1) inhibitor INCB052793 showed encouraging activity, particularly in combination with azacitidine, in certain patients with advanced myeloid malignancies in a phase 1/2 trial.
The activity was seen even in patients who previously failed treatment with hypomethylating agents, Amer M. Zeidan, MD, reported at the annual meeting of the American Society of Hematology.
In the combination therapy dose escalation phase (phase 1b), seven patients with MM received INCB052793 at doses of 25 mg or 35 mg daily plus dexamethasone, and nine patients with acute myeloid leukemia (AML) or MDS received INCB052793 plus azacitidine. During the dose expansion, 12 patients received a daily dose of 35 mg for 28-day cycles plus azacitidine (in AML and MDS patients), according to Dr. Zeidan of Yale University, New Haven, Conn.
The study employed a 3+3 dose-escalation design until dose-limiting toxicities occurred. Patients were treated in continuous cycles until study termination, consent withdrawal, disease progression, or unacceptable toxicity.
Phase 2 of the study is evaluating INCB052793 in combination with azacitidine in nine patients with AML or high-risk MDS who failed prior therapy with hypomethylating agents. The 35-mg daily dose was selected for this phase based on pharmacodynamic effect and the presence of thrombocytopenia in solid tumor patients at higher doses, he said.
At the data cutoff for this preliminary assessment, 1 of the 11 patients who received INCB052793 monotherapy – a patient with MDS/MPN – experienced complete response (CR) and remained on study at the data cutoff. Two monotherapy patients with MDS/MPN experienced partial remission (PR).
Of seven patients with MM in the INCB052793-plus-dexamethasone group, two had a minimal response with a reduction in M protein.
In the INCB052793-plus-azacitidine group, overall response rates were 67% in 12 patients with AML and 56% in patients with MDS or MDS/MPN.
In the AML group, there was one CR, one morphologic leukemia-free state, and two PRs. In the MDS group, three of seven patients had a CR. Among the two patients in the MDS/MPN group, one had a CR and one had a PR.
Of note, none of the seven patients in the INCB052793-plus-dexamethasone group had received prior treatment with hypomethylating agents, while 10 of 21 patients in the INCB052793-plus-azacitidine phase 1b group had, as well as all of the nine phase 2 patients. The results were as of Nov. 3, 2017, Dr. Zeidan said.
The JAK/STAT pathway plays an important role in cytokine and growth factor signal transduction. Dysregulation of the JAK/STAT pathway is associated with the pathogenesis of various hematologic malignancies, Dr. Zeidan explained, noting that blocking JAK signaling can inhibit AML cell proliferation through STAT3/5 inhibition and induction of caspase-dependent apoptosis.
INCB052793 is a small molecule JAK1 inhibitor with potential as monotherapy or in combination with standard therapies for treating advanced hematologic malignancies. It could be of particular benefit for high-risk MDS patients who have failed prior therapy with hypomethylating agents, as these patients have no available standard of care and their overall survival is often less than 6 months, he said.
These preliminary data show that treatment is associated with a number of nonhematologic and hematologic adverse events. Grade 3 or greater adverse events were observed in 45% of patients receiving INCB052793 monotherapy, 86% of patients receiving INCB052793 plus dexamethasone, and 95% of those receiving INCB052793 plus azacitidine.
The most common adverse events with INCB052793 plus dexamethasone were anemia, hypercalcemia, hypophosphatemia, pneumonia, sepsis, and thrombocytopenia. With INCB052793 plus azacitidine, the most common events were febrile neutropenia, anemia, neutropenia, and thrombocytopenia.
Most patients included in the current analysis discontinued treatment, including 91% of INCB052793 monotherapy patients, 100% of INCB052793-plus-dexamethasone patients, and 90% of INCB052793-plus-azacitidine patients. The primary reasons for discontinuation were disease progression or adverse events.
Despite these events, the findings suggest that combination therapy with INCB052793 and azacitidine is promising for patients with advanced myeloid malignancies, Dr. Zeidan said. However, signals of activity were lacking in multiple myeloma or lymphoid malignancies.
The findings of encouraging activity in patients who previously failed on hypomethylating agents are of particular interest, and suggest that INCB052793 might resensitize refractory/relapsed patients to the effects of these agents, Dr. Zeidan noted, concluding that these preliminary safety and efficacy data support further evaluation of INCB052793 in this setting. Enrollment is ongoing in phase 2 of the trial.
This study is sponsored by Incyte. Dr. Zeidan reported serving as a consultant for Incyte and Otsuka and as a member of the speakers bureau for Takeda. He also reported financial relationships with AbbVie, Pfizer, Gilead, Celgene, and Ariad.
SOURCE: Zeidan A et al. ASH 2017 Abstract 640.
REPORTING FROM ASH 2017
Key clinical point:
Major finding: Overall response rates with INCB052793 plus azacitidine were 67% in AML and 56% in MDS or MDS/MPN.
Study details: A phase 1/2 study involving 58 initial patients.
Disclosures: This study is sponsored by Incyte. Dr. Zeidan reported serving as a consultant for Incyte and Otsuka and as a member of the speakers bureau for Takeda. He also reported financial relationships with AbbVie, Pfizer, Gilead, Celgene, and Ariad.
Source: Zeidan A et al. ASH 2017 Abstract 640.
Fetal fibronectin testing is infrequent
Fetal fibronectin testing was linked to longer gestation periods and a lower risk of delivery occurring within 3 days of the first hospital contact, but only about half of women with symptoms of preterm labor (PTL, weeks 24-37) received any testing at all for PTL, and just 14.0% received fFN, according to an analysis of administrative claims data from Medicaid enrollees in Texas.
Fetal fibronectin (fFN) testing can help determine the probability of spontaneous preterm birth in the following 14 days.
The results reinforce the value of fFN in predicting spontaneous preterm birth, but also underline the need for additional testing.
Women who received the fFN test incurred an additional cost of $2,252, compared with those who did not receive the test, but their gestation periods lasted an average of 9 additional days. The researchers point out that a conservative cost of time spent in the neonatal intensive care unit is $3,000-$3,500 per day, so that the increased cost of testing would be likely be offset by cost reductions in preterm births.
The study comprised 29,553 women aged 21 years and older who went to the emergency department or were admitted to the hospital with PTL between Jan. 1, 2012, and May 31, 2015. During the 5 months prior to delivery, 74.0% of the subjects received a PTL diagnosis, and 26.0% were diagnosed with threatened PTL, defined as early, threatened, or false labor. Nearly half of the patients (49.8%) underwent at least one PTL test, most often transvaginal ultrasound (44.1%). Just 14.0% of patients received fFN testing.
The researchers used propensity score matching to account for baseline differences in risk factors for the two groups, creating two groups of 4,098 patients (fFN and non-fFN) for the final cohort study.
Patients who received fFN testing were less likely to deliver during the initial health care visit (45.9% vs. 59.3%; P less than .0001) and had a longer mean time to delivery (24.6 days vs. 15.2 days; P less than .0001). They were less likely to deliver within 3 days of the initial visit (49.1% vs. 63.9%; P less than .0001).
Women who received fFN testing had higher all-cause maternal health care costs ($15,238.20 vs. $12,985.80; P less than .0001).
The study did not include newborn outcomes and health care costs. “It is unknown whether use of fFN testing is associated with improved newborn outcomes; if it is, fFN testing could potentially reduce newborn-incurred costs, offsetting the costs associated with testing,” the authors wrote.
SOURCE: Barner J et al. Am J Manag Care. 2017 Dec;23(19 Suppl):S363-70.
Fetal fibronectin testing was linked to longer gestation periods and a lower risk of delivery occurring within 3 days of the first hospital contact, but only about half of women with symptoms of preterm labor (PTL, weeks 24-37) received any testing at all for PTL, and just 14.0% received fFN, according to an analysis of administrative claims data from Medicaid enrollees in Texas.
Fetal fibronectin (fFN) testing can help determine the probability of spontaneous preterm birth in the following 14 days.
The results reinforce the value of fFN in predicting spontaneous preterm birth, but also underline the need for additional testing.
Women who received the fFN test incurred an additional cost of $2,252, compared with those who did not receive the test, but their gestation periods lasted an average of 9 additional days. The researchers point out that a conservative cost of time spent in the neonatal intensive care unit is $3,000-$3,500 per day, so that the increased cost of testing would be likely be offset by cost reductions in preterm births.
The study comprised 29,553 women aged 21 years and older who went to the emergency department or were admitted to the hospital with PTL between Jan. 1, 2012, and May 31, 2015. During the 5 months prior to delivery, 74.0% of the subjects received a PTL diagnosis, and 26.0% were diagnosed with threatened PTL, defined as early, threatened, or false labor. Nearly half of the patients (49.8%) underwent at least one PTL test, most often transvaginal ultrasound (44.1%). Just 14.0% of patients received fFN testing.
The researchers used propensity score matching to account for baseline differences in risk factors for the two groups, creating two groups of 4,098 patients (fFN and non-fFN) for the final cohort study.
Patients who received fFN testing were less likely to deliver during the initial health care visit (45.9% vs. 59.3%; P less than .0001) and had a longer mean time to delivery (24.6 days vs. 15.2 days; P less than .0001). They were less likely to deliver within 3 days of the initial visit (49.1% vs. 63.9%; P less than .0001).
Women who received fFN testing had higher all-cause maternal health care costs ($15,238.20 vs. $12,985.80; P less than .0001).
The study did not include newborn outcomes and health care costs. “It is unknown whether use of fFN testing is associated with improved newborn outcomes; if it is, fFN testing could potentially reduce newborn-incurred costs, offsetting the costs associated with testing,” the authors wrote.
SOURCE: Barner J et al. Am J Manag Care. 2017 Dec;23(19 Suppl):S363-70.
Fetal fibronectin testing was linked to longer gestation periods and a lower risk of delivery occurring within 3 days of the first hospital contact, but only about half of women with symptoms of preterm labor (PTL, weeks 24-37) received any testing at all for PTL, and just 14.0% received fFN, according to an analysis of administrative claims data from Medicaid enrollees in Texas.
Fetal fibronectin (fFN) testing can help determine the probability of spontaneous preterm birth in the following 14 days.
The results reinforce the value of fFN in predicting spontaneous preterm birth, but also underline the need for additional testing.
Women who received the fFN test incurred an additional cost of $2,252, compared with those who did not receive the test, but their gestation periods lasted an average of 9 additional days. The researchers point out that a conservative cost of time spent in the neonatal intensive care unit is $3,000-$3,500 per day, so that the increased cost of testing would be likely be offset by cost reductions in preterm births.
The study comprised 29,553 women aged 21 years and older who went to the emergency department or were admitted to the hospital with PTL between Jan. 1, 2012, and May 31, 2015. During the 5 months prior to delivery, 74.0% of the subjects received a PTL diagnosis, and 26.0% were diagnosed with threatened PTL, defined as early, threatened, or false labor. Nearly half of the patients (49.8%) underwent at least one PTL test, most often transvaginal ultrasound (44.1%). Just 14.0% of patients received fFN testing.
The researchers used propensity score matching to account for baseline differences in risk factors for the two groups, creating two groups of 4,098 patients (fFN and non-fFN) for the final cohort study.
Patients who received fFN testing were less likely to deliver during the initial health care visit (45.9% vs. 59.3%; P less than .0001) and had a longer mean time to delivery (24.6 days vs. 15.2 days; P less than .0001). They were less likely to deliver within 3 days of the initial visit (49.1% vs. 63.9%; P less than .0001).
Women who received fFN testing had higher all-cause maternal health care costs ($15,238.20 vs. $12,985.80; P less than .0001).
The study did not include newborn outcomes and health care costs. “It is unknown whether use of fFN testing is associated with improved newborn outcomes; if it is, fFN testing could potentially reduce newborn-incurred costs, offsetting the costs associated with testing,” the authors wrote.
SOURCE: Barner J et al. Am J Manag Care. 2017 Dec;23(19 Suppl):S363-70.
FROM THE AMERICAN JOURNAL OF MANAGED CARE
Key clinical point: Fetal fibronectin testing in women presenting with preterm labor improves delivery outcomes, but is rarely applied in at-risk women.
Major finding: Fourteen percent of women who presented with symptoms of preterm labor received the fetal fibronectin test.
Data source: Retrospective analysis of claims data among Medicaid recipients in Texas (n = 29,553).
Disclosures: The study was funded by Hologic, which markets the Fetal Fibronectin Enzyme immunoassay and Rapid fFN Test. Some of the authors have financial ties to Hologic.
Source: Barner J et al. Am J Manag Care. 2017 Dec;23(19 Suppl):S363-70.
Iodine deficiency linked to delay in pregnancy
Iodine deficiency could lead to significant delays in becoming pregnant, according to data from a prospective cohort study published online in Human Reproduction.
Researchers followed 501 couples that were discontinuing contraception to become pregnant, for 12 months, with the woman’s iodine levels measured at the time of enrollment.
This negative impact on fecundity remained even after researchers controlled for hypo/hyperthyroidism and adjusted for body mass index and cotinine as an indicator of smoking status.
“The significant delay in time to pregnancy in that group raises serious concerns given the high prevalence of iodine deficiency in women of childbearing age,” wrote James L. Mills, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and his coauthors. Previous research has found that around one-third of American women of childbearing age have urinary iodine concentrations below 100 mcg/L, and iodine deficiency may be present in more than two-thirds of British schoolgirls.
“Although it seems incongruous that deficiency would be common in a population with high sodium intake, the likely explanation is that most sodium in the diet comes from processed food, and it appears that most salt in processed food is not iodized,” they wrote.
Women with iodine-creatinine ratios in the 50-99 mcg/g range – categorized as mildly deficient – had a smaller but nonsignificant increase in time to pregnancy, compared with women with ratios above 100 mcg/g.
Iodine deficiency is known to have effects on thyroid function, and hypothyroidism in particular is associated with infertility, the authors wrote.
“Low thyroid hormone concentrations are associated with thyrotropin-releasing hormone elevations that stimulate prolactin, which in turn interferes with GnRH pulsatility,” they wrote. “They also cause decreased granulosa cell steroid production and alterations in androgen and estrogen concentrations.”
The researchers selected couples that had recently stopped using contraception to rule out individuals with long-term fertility problems. They also used sensitive HCG pregnancy tests, and the women kept daily journals so that the time to pregnancy could be calculated accurately.
However, they did note that iodine levels were measured only at enrollment and may have varied over the course of the study. They also did not measure thyroid levels during the study.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. No conflicts of interest were declared.
SOURCE: Mills JL et al. Hum Reprod. 2018 Jan 11. doi: 10.1093/humrep/dex379.
Iodine deficiency could lead to significant delays in becoming pregnant, according to data from a prospective cohort study published online in Human Reproduction.
Researchers followed 501 couples that were discontinuing contraception to become pregnant, for 12 months, with the woman’s iodine levels measured at the time of enrollment.
This negative impact on fecundity remained even after researchers controlled for hypo/hyperthyroidism and adjusted for body mass index and cotinine as an indicator of smoking status.
“The significant delay in time to pregnancy in that group raises serious concerns given the high prevalence of iodine deficiency in women of childbearing age,” wrote James L. Mills, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and his coauthors. Previous research has found that around one-third of American women of childbearing age have urinary iodine concentrations below 100 mcg/L, and iodine deficiency may be present in more than two-thirds of British schoolgirls.
“Although it seems incongruous that deficiency would be common in a population with high sodium intake, the likely explanation is that most sodium in the diet comes from processed food, and it appears that most salt in processed food is not iodized,” they wrote.
Women with iodine-creatinine ratios in the 50-99 mcg/g range – categorized as mildly deficient – had a smaller but nonsignificant increase in time to pregnancy, compared with women with ratios above 100 mcg/g.
Iodine deficiency is known to have effects on thyroid function, and hypothyroidism in particular is associated with infertility, the authors wrote.
“Low thyroid hormone concentrations are associated with thyrotropin-releasing hormone elevations that stimulate prolactin, which in turn interferes with GnRH pulsatility,” they wrote. “They also cause decreased granulosa cell steroid production and alterations in androgen and estrogen concentrations.”
The researchers selected couples that had recently stopped using contraception to rule out individuals with long-term fertility problems. They also used sensitive HCG pregnancy tests, and the women kept daily journals so that the time to pregnancy could be calculated accurately.
However, they did note that iodine levels were measured only at enrollment and may have varied over the course of the study. They also did not measure thyroid levels during the study.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. No conflicts of interest were declared.
SOURCE: Mills JL et al. Hum Reprod. 2018 Jan 11. doi: 10.1093/humrep/dex379.
Iodine deficiency could lead to significant delays in becoming pregnant, according to data from a prospective cohort study published online in Human Reproduction.
Researchers followed 501 couples that were discontinuing contraception to become pregnant, for 12 months, with the woman’s iodine levels measured at the time of enrollment.
This negative impact on fecundity remained even after researchers controlled for hypo/hyperthyroidism and adjusted for body mass index and cotinine as an indicator of smoking status.
“The significant delay in time to pregnancy in that group raises serious concerns given the high prevalence of iodine deficiency in women of childbearing age,” wrote James L. Mills, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and his coauthors. Previous research has found that around one-third of American women of childbearing age have urinary iodine concentrations below 100 mcg/L, and iodine deficiency may be present in more than two-thirds of British schoolgirls.
“Although it seems incongruous that deficiency would be common in a population with high sodium intake, the likely explanation is that most sodium in the diet comes from processed food, and it appears that most salt in processed food is not iodized,” they wrote.
Women with iodine-creatinine ratios in the 50-99 mcg/g range – categorized as mildly deficient – had a smaller but nonsignificant increase in time to pregnancy, compared with women with ratios above 100 mcg/g.
Iodine deficiency is known to have effects on thyroid function, and hypothyroidism in particular is associated with infertility, the authors wrote.
“Low thyroid hormone concentrations are associated with thyrotropin-releasing hormone elevations that stimulate prolactin, which in turn interferes with GnRH pulsatility,” they wrote. “They also cause decreased granulosa cell steroid production and alterations in androgen and estrogen concentrations.”
The researchers selected couples that had recently stopped using contraception to rule out individuals with long-term fertility problems. They also used sensitive HCG pregnancy tests, and the women kept daily journals so that the time to pregnancy could be calculated accurately.
However, they did note that iodine levels were measured only at enrollment and may have varied over the course of the study. They also did not measure thyroid levels during the study.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. No conflicts of interest were declared.
SOURCE: Mills JL et al. Hum Reprod. 2018 Jan 11. doi: 10.1093/humrep/dex379.
FROM HUMAN REPRODUCTION
Key clinical point: Women with moderate to severe iodine deficiency could experience significant delays in time to achieving pregnancy.
Major finding: Women with iodine levels in the moderate to severe range showed a 44% lower odds ratio of becoming pregnant in any one cycle, compared with women with levels in the normal range.
Data source: Population-based prospective cohort study in 501 couples.
Disclosures: The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. No conflicts of interest were declared.
Source: Hum Reprod. 2018 Jan. doi: 10.1093/humrep/dex379.
DMARDs may hamper pneumococcal vaccine response in systemic sclerosis patients
Patients taking disease-modifying antirheumatic medications for systemic sclerosis appear to have a decreased response to pneumococcal vaccines, a Swedish study has determined.
Those not taking disease-modifying antirheumatic medications (DMARDs), however, had a normal immune response, suggesting that it’s the immunomodulating medications, not the disease itself, that is affecting antibody levels, Roger Hesselstrand, MD, of Lund (Sweden) University and his colleagues reported online in Rheumatology.
“The currently recommended prime-boost vaccination strategy using a dose of PCV13 [13-valent pneumococcal conjugate vaccine] followed by a dose of PPV23 [23-valent pneumococcal polysaccharide vaccine] might be a possible way of enhancing the vaccine immunogenicity in immunosuppressed patients,” Dr. Hesselstrand and his coauthors wrote.
The study comprised 44 subjects with systemic sclerosis, 12 of whom were taking a DMARD (mycophenolate mofetil, azathioprine, or hydroxychloroquine), and 49 healthy controls; all underwent pneumococcal vaccination. The first 13 got a single dose of PPV23 intramuscularly. PCV13 was then licensed for adults in Sweden, and the remaining 31 patients received this vaccine. The primary outcome was 6-week change from baseline in the level of pneumococcal IgG to Streptococcus pneumoniae serotypes 23F and 6B.
Both vaccines were safe and well-tolerated by all patients, including those taking a DMARD.
Before vaccination, antibody levels to both serotypes were similar between the groups. After vaccination, antibody levels for both serotypes increased significantly in systemic sclerosis patients not taking a DMARD and in controls. However, patients taking a DMARD mounted only an adequate response to serotype 6B.
There were fewer responders among those taking DMARDs, whether they received the PCV13 or the PPV23 vaccine. An increase from prevaccination antibody levels of at least twofold occurred in fewer patients taking DMARDs than did in patients not taking DMARDs and in controls, regardless of vaccine type (PPV23, 50% vs. about 55% and 50%, respectively; PCV13, about 17% vs. 57% and 100%, respectively).
“We demonstrated that the antibody response ... as well as functionality of antibodies in [systemic sclerosis] patients not receiving DMARDs was as good as in controls regardless of vaccine type,” the investigators concluded. “Systemic sclerosis patients treated with DMARDs, however, had lower proportion of patients with positive antibody response, although the functionality of the antibodies was preserved. These results suggest that immunomodulating drugs but not systemic sclerosis itself and/or immunological disturbance as a part of this disease affect the ability to produce a sufficient amount of vaccine-specific antibodies, but not their function.”
None of the authors had conflicts of interest to disclose.
SOURCE: Hesselstrand R et al. Rheumatology [Oxford]. 2018 Jan 8. doi: 10.1093/rheumatology/kex471.
Patients taking disease-modifying antirheumatic medications for systemic sclerosis appear to have a decreased response to pneumococcal vaccines, a Swedish study has determined.
Those not taking disease-modifying antirheumatic medications (DMARDs), however, had a normal immune response, suggesting that it’s the immunomodulating medications, not the disease itself, that is affecting antibody levels, Roger Hesselstrand, MD, of Lund (Sweden) University and his colleagues reported online in Rheumatology.
“The currently recommended prime-boost vaccination strategy using a dose of PCV13 [13-valent pneumococcal conjugate vaccine] followed by a dose of PPV23 [23-valent pneumococcal polysaccharide vaccine] might be a possible way of enhancing the vaccine immunogenicity in immunosuppressed patients,” Dr. Hesselstrand and his coauthors wrote.
The study comprised 44 subjects with systemic sclerosis, 12 of whom were taking a DMARD (mycophenolate mofetil, azathioprine, or hydroxychloroquine), and 49 healthy controls; all underwent pneumococcal vaccination. The first 13 got a single dose of PPV23 intramuscularly. PCV13 was then licensed for adults in Sweden, and the remaining 31 patients received this vaccine. The primary outcome was 6-week change from baseline in the level of pneumococcal IgG to Streptococcus pneumoniae serotypes 23F and 6B.
Both vaccines were safe and well-tolerated by all patients, including those taking a DMARD.
Before vaccination, antibody levels to both serotypes were similar between the groups. After vaccination, antibody levels for both serotypes increased significantly in systemic sclerosis patients not taking a DMARD and in controls. However, patients taking a DMARD mounted only an adequate response to serotype 6B.
There were fewer responders among those taking DMARDs, whether they received the PCV13 or the PPV23 vaccine. An increase from prevaccination antibody levels of at least twofold occurred in fewer patients taking DMARDs than did in patients not taking DMARDs and in controls, regardless of vaccine type (PPV23, 50% vs. about 55% and 50%, respectively; PCV13, about 17% vs. 57% and 100%, respectively).
“We demonstrated that the antibody response ... as well as functionality of antibodies in [systemic sclerosis] patients not receiving DMARDs was as good as in controls regardless of vaccine type,” the investigators concluded. “Systemic sclerosis patients treated with DMARDs, however, had lower proportion of patients with positive antibody response, although the functionality of the antibodies was preserved. These results suggest that immunomodulating drugs but not systemic sclerosis itself and/or immunological disturbance as a part of this disease affect the ability to produce a sufficient amount of vaccine-specific antibodies, but not their function.”
None of the authors had conflicts of interest to disclose.
SOURCE: Hesselstrand R et al. Rheumatology [Oxford]. 2018 Jan 8. doi: 10.1093/rheumatology/kex471.
Patients taking disease-modifying antirheumatic medications for systemic sclerosis appear to have a decreased response to pneumococcal vaccines, a Swedish study has determined.
Those not taking disease-modifying antirheumatic medications (DMARDs), however, had a normal immune response, suggesting that it’s the immunomodulating medications, not the disease itself, that is affecting antibody levels, Roger Hesselstrand, MD, of Lund (Sweden) University and his colleagues reported online in Rheumatology.
“The currently recommended prime-boost vaccination strategy using a dose of PCV13 [13-valent pneumococcal conjugate vaccine] followed by a dose of PPV23 [23-valent pneumococcal polysaccharide vaccine] might be a possible way of enhancing the vaccine immunogenicity in immunosuppressed patients,” Dr. Hesselstrand and his coauthors wrote.
The study comprised 44 subjects with systemic sclerosis, 12 of whom were taking a DMARD (mycophenolate mofetil, azathioprine, or hydroxychloroquine), and 49 healthy controls; all underwent pneumococcal vaccination. The first 13 got a single dose of PPV23 intramuscularly. PCV13 was then licensed for adults in Sweden, and the remaining 31 patients received this vaccine. The primary outcome was 6-week change from baseline in the level of pneumococcal IgG to Streptococcus pneumoniae serotypes 23F and 6B.
Both vaccines were safe and well-tolerated by all patients, including those taking a DMARD.
Before vaccination, antibody levels to both serotypes were similar between the groups. After vaccination, antibody levels for both serotypes increased significantly in systemic sclerosis patients not taking a DMARD and in controls. However, patients taking a DMARD mounted only an adequate response to serotype 6B.
There were fewer responders among those taking DMARDs, whether they received the PCV13 or the PPV23 vaccine. An increase from prevaccination antibody levels of at least twofold occurred in fewer patients taking DMARDs than did in patients not taking DMARDs and in controls, regardless of vaccine type (PPV23, 50% vs. about 55% and 50%, respectively; PCV13, about 17% vs. 57% and 100%, respectively).
“We demonstrated that the antibody response ... as well as functionality of antibodies in [systemic sclerosis] patients not receiving DMARDs was as good as in controls regardless of vaccine type,” the investigators concluded. “Systemic sclerosis patients treated with DMARDs, however, had lower proportion of patients with positive antibody response, although the functionality of the antibodies was preserved. These results suggest that immunomodulating drugs but not systemic sclerosis itself and/or immunological disturbance as a part of this disease affect the ability to produce a sufficient amount of vaccine-specific antibodies, but not their function.”
None of the authors had conflicts of interest to disclose.
SOURCE: Hesselstrand R et al. Rheumatology [Oxford]. 2018 Jan 8. doi: 10.1093/rheumatology/kex471.
FROM RHEUMATOLOGY
Key clinical point:
Major finding: An increase in prevaccination antibody levels of at least twofold occurred in significantly fewer patients taking DMARDs than in patients not taking DMARDs and controls, regardless of vaccine type (PPV23, 50% vs. about 55% and 50%, respectively; PCV13, about 17% vs. 57% and 100%, respectively).
Study details: The prospective study comprised 44 systemic sclerosis patients and 49 healthy controls.
Disclosures: None of the authors had conflicts of interest to disclose.
Source: Hesselstrand R et al. Rheumatology [Oxford]. 2018 Jan 8. doi: 10.1093/rheumatology/kex471
Immune-modified RECIST can help identify survival benefit from cancer immunotherapy
Cancer immunotherapy-specific response criteria not only provide improved estimates of treatment response versus standard criteria, but may also better identify patients who achieve an overall survival benefit from therapy.
Compared to standard Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, the immune-modified RECIST provided a 1%-2% greater overall response and an 8%-13% greater rate of disease control, and added 0.5-1.5 months to median progression-free survival among patients treated with the PD-L1 inhibitor atezolizumab, according to analyses of different phase 1 and 2 trials.
In addition, overall survival (OS) benefit in some of the trials could be better delineated using the immune-modified criteria, which account for unique patterns of progression sometimes experienced by patients on cancer immunotherapy, noted the study authors. The report was published in the Journal of Clinical Oncology.
Using immune-specific criteria to evaluate response to cancer immunotherapy is not a new concept. However, there are only limited data on how those criteria might apply to predictions of OS, according to lead author F. Stephen Hodi, MD, of Dana-Farber Cancer Institute, Boston, and his coauthors.
“These analyses reveal aspects of immune-modified RECIST that seem to predict OS better than RECIST v1.1, and aspects needing refinement to improve the ability to predict clinical benefit,” wrote Dr. Hodi and his colleagues.
Typical response criteria may not adequately predict the potential OS benefit of cancer immunotherapy, since patients receiving cancer immunotherapy may exhibit response patterns outside of the “classic response patterns” seen with other anticancer treatments, they noted.
In particular, some patients may experience an initial transient increase in tumor burden before responding, while in other cases, patients with responding baseline lesions might develop new lesions.
Immune-modified criteria have been developed to account for those “other patterns” that can manifest with cancer immunotherapy, the authors said.
Dr. Hodi and his colleagues sought to evaluate outcomes by RECIST vs. immune-related RECIST criteria among patients treated with atezolizumab in studies of non–small-cell lung cancer (NSCLC) and metastatic urothelial carcinoma.
In the phase 2 BIRCH study of first-line atezolizumab for NSCLC, they found that immune-related RECIST criteria appeared to predict OS better than RECIST. Median overall survival was 4.0 months longer among patients who had progressive disease (PD) by RECIST criteria within 90 days of study enrollment, versus patients who had PD by both RECIST and immune-modified RECIST at that time point, Dr. Hodi and his colleagues reported.
In the POPLAR trial of atezolizumab in NSCLC, median overall survival was 1.4 months longer for patients with PD by RECIST vs. patients with PD by both RECIST and immune-modified RECIST at 90 days, they reported.
For patients with metastatic urothelial bladder cancer treated with atezolizumab in the IMvigor210 study, median overall survival was 4.4 months longer for patients with PD by RECIST only vs. PD by both RECIST and immune-related RECIST within 180 days of enrollment, the researchers noted.
An international effort is underway to compare data sets from larger trial sets and multiple cancer immunotherapy agents, they wrote.
SOURCE: Hodi FS et al., J Clin Oncol. 2018 Jan 17. doi: 10.1200/JCO.2017.75.1644
Cancer immunotherapy-specific response criteria not only provide improved estimates of treatment response versus standard criteria, but may also better identify patients who achieve an overall survival benefit from therapy.
Compared to standard Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, the immune-modified RECIST provided a 1%-2% greater overall response and an 8%-13% greater rate of disease control, and added 0.5-1.5 months to median progression-free survival among patients treated with the PD-L1 inhibitor atezolizumab, according to analyses of different phase 1 and 2 trials.
In addition, overall survival (OS) benefit in some of the trials could be better delineated using the immune-modified criteria, which account for unique patterns of progression sometimes experienced by patients on cancer immunotherapy, noted the study authors. The report was published in the Journal of Clinical Oncology.
Using immune-specific criteria to evaluate response to cancer immunotherapy is not a new concept. However, there are only limited data on how those criteria might apply to predictions of OS, according to lead author F. Stephen Hodi, MD, of Dana-Farber Cancer Institute, Boston, and his coauthors.
“These analyses reveal aspects of immune-modified RECIST that seem to predict OS better than RECIST v1.1, and aspects needing refinement to improve the ability to predict clinical benefit,” wrote Dr. Hodi and his colleagues.
Typical response criteria may not adequately predict the potential OS benefit of cancer immunotherapy, since patients receiving cancer immunotherapy may exhibit response patterns outside of the “classic response patterns” seen with other anticancer treatments, they noted.
In particular, some patients may experience an initial transient increase in tumor burden before responding, while in other cases, patients with responding baseline lesions might develop new lesions.
Immune-modified criteria have been developed to account for those “other patterns” that can manifest with cancer immunotherapy, the authors said.
Dr. Hodi and his colleagues sought to evaluate outcomes by RECIST vs. immune-related RECIST criteria among patients treated with atezolizumab in studies of non–small-cell lung cancer (NSCLC) and metastatic urothelial carcinoma.
In the phase 2 BIRCH study of first-line atezolizumab for NSCLC, they found that immune-related RECIST criteria appeared to predict OS better than RECIST. Median overall survival was 4.0 months longer among patients who had progressive disease (PD) by RECIST criteria within 90 days of study enrollment, versus patients who had PD by both RECIST and immune-modified RECIST at that time point, Dr. Hodi and his colleagues reported.
In the POPLAR trial of atezolizumab in NSCLC, median overall survival was 1.4 months longer for patients with PD by RECIST vs. patients with PD by both RECIST and immune-modified RECIST at 90 days, they reported.
For patients with metastatic urothelial bladder cancer treated with atezolizumab in the IMvigor210 study, median overall survival was 4.4 months longer for patients with PD by RECIST only vs. PD by both RECIST and immune-related RECIST within 180 days of enrollment, the researchers noted.
An international effort is underway to compare data sets from larger trial sets and multiple cancer immunotherapy agents, they wrote.
SOURCE: Hodi FS et al., J Clin Oncol. 2018 Jan 17. doi: 10.1200/JCO.2017.75.1644
Cancer immunotherapy-specific response criteria not only provide improved estimates of treatment response versus standard criteria, but may also better identify patients who achieve an overall survival benefit from therapy.
Compared to standard Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, the immune-modified RECIST provided a 1%-2% greater overall response and an 8%-13% greater rate of disease control, and added 0.5-1.5 months to median progression-free survival among patients treated with the PD-L1 inhibitor atezolizumab, according to analyses of different phase 1 and 2 trials.
In addition, overall survival (OS) benefit in some of the trials could be better delineated using the immune-modified criteria, which account for unique patterns of progression sometimes experienced by patients on cancer immunotherapy, noted the study authors. The report was published in the Journal of Clinical Oncology.
Using immune-specific criteria to evaluate response to cancer immunotherapy is not a new concept. However, there are only limited data on how those criteria might apply to predictions of OS, according to lead author F. Stephen Hodi, MD, of Dana-Farber Cancer Institute, Boston, and his coauthors.
“These analyses reveal aspects of immune-modified RECIST that seem to predict OS better than RECIST v1.1, and aspects needing refinement to improve the ability to predict clinical benefit,” wrote Dr. Hodi and his colleagues.
Typical response criteria may not adequately predict the potential OS benefit of cancer immunotherapy, since patients receiving cancer immunotherapy may exhibit response patterns outside of the “classic response patterns” seen with other anticancer treatments, they noted.
In particular, some patients may experience an initial transient increase in tumor burden before responding, while in other cases, patients with responding baseline lesions might develop new lesions.
Immune-modified criteria have been developed to account for those “other patterns” that can manifest with cancer immunotherapy, the authors said.
Dr. Hodi and his colleagues sought to evaluate outcomes by RECIST vs. immune-related RECIST criteria among patients treated with atezolizumab in studies of non–small-cell lung cancer (NSCLC) and metastatic urothelial carcinoma.
In the phase 2 BIRCH study of first-line atezolizumab for NSCLC, they found that immune-related RECIST criteria appeared to predict OS better than RECIST. Median overall survival was 4.0 months longer among patients who had progressive disease (PD) by RECIST criteria within 90 days of study enrollment, versus patients who had PD by both RECIST and immune-modified RECIST at that time point, Dr. Hodi and his colleagues reported.
In the POPLAR trial of atezolizumab in NSCLC, median overall survival was 1.4 months longer for patients with PD by RECIST vs. patients with PD by both RECIST and immune-modified RECIST at 90 days, they reported.
For patients with metastatic urothelial bladder cancer treated with atezolizumab in the IMvigor210 study, median overall survival was 4.4 months longer for patients with PD by RECIST only vs. PD by both RECIST and immune-related RECIST within 180 days of enrollment, the researchers noted.
An international effort is underway to compare data sets from larger trial sets and multiple cancer immunotherapy agents, they wrote.
SOURCE: Hodi FS et al., J Clin Oncol. 2018 Jan 17. doi: 10.1200/JCO.2017.75.1644
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Compared to standard criteria for response evaluation, criteria developed specifically to evaluate response to cancer immunotherapy better identified patients with an overall survival (OS) benefit.
Major finding: Median OS was 4.0 and 1.4 months longer, respectively, in the BIRCH and POPLAR non–small-cell lung cancer trial among patients who had progressive disease (PD) by standard criteria only, as opposed to patients who also had PD according to the immunotherapy-specific response criteria.
Data source: Analysis of patients treated with single-agent atezolizumab in phase 1 and 2 clinical trials.
Disclosures: The study was supported by F. Hoffmann-La Roche. Authors reported disclosures related to Merck Sharp & Dohme, Novartis, Genentech/Roche, Bristol-Myers Squibb, and others.
Source: Hodi FS et al., J Clin Oncol. 2018 Jan 17. doi: 10.1200/JCO.2017.75.1644.
Papules below eyes
The FP looked at the small papules closely and recognized them as white milia cysts and flesh-colored syringomas. He explained to the patient that both conditions were benign and discussed treatment options.
Milia cysts, which appear as shiny white papules, can be extracted. This procedure is performed without local anesthesia, and the most uncomfortable part is when pressure is applied with the comedone extractor against the infraorbital bone. (The billing code for this procedure is the same as the one used for acne surgery.)
Syringomas, however, are not easily treated. New lesions can form even if some resolve. Treatment options for syringomas include topical trichloroacetic acid, cryosurgery, and electrosurgery. Because this patient’s lesions were on the eyelids, as they often are, there are risks involved.
The patient agreed to extraction of the milia cysts, so the FP removed a number of them using the tip of a Number 11 scalpel blade and a comedone extractor. The patient was happy to have them removed and said that he would think about the options for syringoma treatment at a future date.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Sebaceous hyperplasia. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 931-934.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP looked at the small papules closely and recognized them as white milia cysts and flesh-colored syringomas. He explained to the patient that both conditions were benign and discussed treatment options.
Milia cysts, which appear as shiny white papules, can be extracted. This procedure is performed without local anesthesia, and the most uncomfortable part is when pressure is applied with the comedone extractor against the infraorbital bone. (The billing code for this procedure is the same as the one used for acne surgery.)
Syringomas, however, are not easily treated. New lesions can form even if some resolve. Treatment options for syringomas include topical trichloroacetic acid, cryosurgery, and electrosurgery. Because this patient’s lesions were on the eyelids, as they often are, there are risks involved.
The patient agreed to extraction of the milia cysts, so the FP removed a number of them using the tip of a Number 11 scalpel blade and a comedone extractor. The patient was happy to have them removed and said that he would think about the options for syringoma treatment at a future date.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Sebaceous hyperplasia. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 931-934.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP looked at the small papules closely and recognized them as white milia cysts and flesh-colored syringomas. He explained to the patient that both conditions were benign and discussed treatment options.
Milia cysts, which appear as shiny white papules, can be extracted. This procedure is performed without local anesthesia, and the most uncomfortable part is when pressure is applied with the comedone extractor against the infraorbital bone. (The billing code for this procedure is the same as the one used for acne surgery.)
Syringomas, however, are not easily treated. New lesions can form even if some resolve. Treatment options for syringomas include topical trichloroacetic acid, cryosurgery, and electrosurgery. Because this patient’s lesions were on the eyelids, as they often are, there are risks involved.
The patient agreed to extraction of the milia cysts, so the FP removed a number of them using the tip of a Number 11 scalpel blade and a comedone extractor. The patient was happy to have them removed and said that he would think about the options for syringoma treatment at a future date.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Sebaceous hyperplasia. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 931-934.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
Ixekizumab beats ustekinumab for fingernail psoriasis, hands down
GENEVA – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.
He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial. The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab (Br J Dermatol. 2017 Oct;177[4]:1014-23).
However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.
By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.
Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.
At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.
This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.
SOURCE: Dutronc Y. https://eadvgeneva2017.org/
GENEVA – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.
He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial. The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab (Br J Dermatol. 2017 Oct;177[4]:1014-23).
However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.
By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.
Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.
At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.
This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.
SOURCE: Dutronc Y. https://eadvgeneva2017.org/
GENEVA – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.
He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial. The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab (Br J Dermatol. 2017 Oct;177[4]:1014-23).
However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.
By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.
Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.
At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.
This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.
SOURCE: Dutronc Y. https://eadvgeneva2017.org/
REPORTING FROM THE EADV CONGRESS
Key clinical point:
Major finding: At week 24, complete clearance of fingernail psoriasis was documented in 49% of patients on ixekizumab and 23% on ustekinumab.
Study details: This secondary analysis of the randomized, multicenter, prospective, phase 3b IXORA-S trial included 189 patients with moderate to severe plaque psoriasis with fingernail involvement.
Disclosures: The study was sponsored by Eli Lilly and presented by a company employee.
Source: Dutronc Y. https://eadvgeneva2017.org