University of Manchester

The antimicrobial agent triclosan may be able to fight drug-resistant malaria, according to research published in Scientific Reports.

For this work, researchers used an artificially intelligent “robot scientist” named Eve to perform a high-throughput screen of potential antimalarial compounds.

The screen revealed that triclosan is effective against Plasmodium parasites that have grown resistant to the antimalarial drug pyrimethamine.

Researchers have known for some time that triclosan inhibits in vitro growth of Plasmodium parasites. They assumed this was because triclosan inhibits the enzyme enoyl reductase (ENR).

However, subsequent work showed that improving triclosan’s ability to target ENR had no effect on parasite growth in the blood.

With the current study, researchers discovered that triclosan also affects parasite growth by inhibiting an enzyme called dihydrofolate reductase (DHFR), which is the target of the antimalarial drug pyrimethamine.

The researchers conducted growth competition experiments with 3 yeast strains dependent on a DHFR enzyme from Plasmodium falciparum, a DHFR enzyme from Plasmodium vivax, and human DHFR.

The team used Eve to screen compounds and identify drugs that inhibit the parasite targets but not the human counterpart.

The researchers found that triclosan was able to target and act on DHFR in both wild-type and pyrimethamine-resistant P falciparum and P vivax parasites.

Because triclosan inhibits both ENR and DHFR, the researchers think it may be possible to target Plasmodium parasites at both the liver and blood stages.

“The discovery by our robot ‘colleague’ Eve that triclosan is effective against malaria targets offers hope that we may be able to use it to develop a new drug,” said study author Elizabeth Bilsland, PhD, of the University of Campinas in Brazil.

“We know it is a safe compound, and its ability to target 2 points in the malaria parasite’s life-cycle means the parasite will find it difficult to evolve resistance.”

Eve was developed to speed up the drug discovery process by automatically developing and testing hypotheses to explain observations, run experiments using laboratory robotics, interpret the results to amend hypotheses, and then repeat the cycle.

“Artificial intelligence and machine-learning enables us to create automated scientists that do not just take a ‘brute force’ approach but, rather, take an intelligent approach to science,” said Ross King, PhD, a professor at the University of Manchester in the UK who led the development of Eve.

“This could greatly speed up the drug discovery process and potentially reap huge rewards.”

University of Manchester

The antimicrobial agent triclosan may be able to fight drug-resistant malaria, according to research published in Scientific Reports.

For this work, researchers used an artificially intelligent “robot scientist” named Eve to perform a high-throughput screen of potential antimalarial compounds.

The screen revealed that triclosan is effective against Plasmodium parasites that have grown resistant to the antimalarial drug pyrimethamine.

Researchers have known for some time that triclosan inhibits in vitro growth of Plasmodium parasites. They assumed this was because triclosan inhibits the enzyme enoyl reductase (ENR).

However, subsequent work showed that improving triclosan’s ability to target ENR had no effect on parasite growth in the blood.

With the current study, researchers discovered that triclosan also affects parasite growth by inhibiting an enzyme called dihydrofolate reductase (DHFR), which is the target of the antimalarial drug pyrimethamine.

The researchers conducted growth competition experiments with 3 yeast strains dependent on a DHFR enzyme from Plasmodium falciparum, a DHFR enzyme from Plasmodium vivax, and human DHFR.

The team used Eve to screen compounds and identify drugs that inhibit the parasite targets but not the human counterpart.

The researchers found that triclosan was able to target and act on DHFR in both wild-type and pyrimethamine-resistant P falciparum and P vivax parasites.

Because triclosan inhibits both ENR and DHFR, the researchers think it may be possible to target Plasmodium parasites at both the liver and blood stages.

“The discovery by our robot ‘colleague’ Eve that triclosan is effective against malaria targets offers hope that we may be able to use it to develop a new drug,” said study author Elizabeth Bilsland, PhD, of the University of Campinas in Brazil.

“We know it is a safe compound, and its ability to target 2 points in the malaria parasite’s life-cycle means the parasite will find it difficult to evolve resistance.”

Eve was developed to speed up the drug discovery process by automatically developing and testing hypotheses to explain observations, run experiments using laboratory robotics, interpret the results to amend hypotheses, and then repeat the cycle.

“Artificial intelligence and machine-learning enables us to create automated scientists that do not just take a ‘brute force’ approach but, rather, take an intelligent approach to science,” said Ross King, PhD, a professor at the University of Manchester in the UK who led the development of Eve.

“This could greatly speed up the drug discovery process and potentially reap huge rewards.”

University of Manchester

The antimicrobial agent triclosan may be able to fight drug-resistant malaria, according to research published in Scientific Reports.

For this work, researchers used an artificially intelligent “robot scientist” named Eve to perform a high-throughput screen of potential antimalarial compounds.

The screen revealed that triclosan is effective against Plasmodium parasites that have grown resistant to the antimalarial drug pyrimethamine.

Researchers have known for some time that triclosan inhibits in vitro growth of Plasmodium parasites. They assumed this was because triclosan inhibits the enzyme enoyl reductase (ENR).

However, subsequent work showed that improving triclosan’s ability to target ENR had no effect on parasite growth in the blood.

With the current study, researchers discovered that triclosan also affects parasite growth by inhibiting an enzyme called dihydrofolate reductase (DHFR), which is the target of the antimalarial drug pyrimethamine.

The researchers conducted growth competition experiments with 3 yeast strains dependent on a DHFR enzyme from Plasmodium falciparum, a DHFR enzyme from Plasmodium vivax, and human DHFR.

The team used Eve to screen compounds and identify drugs that inhibit the parasite targets but not the human counterpart.

The researchers found that triclosan was able to target and act on DHFR in both wild-type and pyrimethamine-resistant P falciparum and P vivax parasites.

Because triclosan inhibits both ENR and DHFR, the researchers think it may be possible to target Plasmodium parasites at both the liver and blood stages.

“The discovery by our robot ‘colleague’ Eve that triclosan is effective against malaria targets offers hope that we may be able to use it to develop a new drug,” said study author Elizabeth Bilsland, PhD, of the University of Campinas in Brazil.

“We know it is a safe compound, and its ability to target 2 points in the malaria parasite’s life-cycle means the parasite will find it difficult to evolve resistance.”

Eve was developed to speed up the drug discovery process by automatically developing and testing hypotheses to explain observations, run experiments using laboratory robotics, interpret the results to amend hypotheses, and then repeat the cycle.

“Artificial intelligence and machine-learning enables us to create automated scientists that do not just take a ‘brute force’ approach but, rather, take an intelligent approach to science,” said Ross King, PhD, a professor at the University of Manchester in the UK who led the development of Eve.

“This could greatly speed up the drug discovery process and potentially reap huge rewards.”

Brief primary care cognitive-behavioral therapy (CBT) among youth who decline antidepressant therapy appears cost-effective, results of a study found.

“In this study, we demonstrate that brief primary care CBT is a cost-effective treatment option for adolescents with depression and likely generates cost savings over 2 years,” said John F. Dickerson, PhD, of Kaiser Permanente Center for Health Research, Portland, Ore., and his associates

Rawpixel/Thinkstock

Brief primary care cognitive-behavioral therapy (CBT) among youth who decline antidepressant therapy appears cost-effective, results of a study found.

“In this study, we demonstrate that brief primary care CBT is a cost-effective treatment option for adolescents with depression and likely generates cost savings over 2 years,” said John F. Dickerson, PhD, of Kaiser Permanente Center for Health Research, Portland, Ore., and his associates

Rawpixel/Thinkstock

Brief primary care cognitive-behavioral therapy (CBT) among youth who decline antidepressant therapy appears cost-effective, results of a study found.

“In this study, we demonstrate that brief primary care CBT is a cost-effective treatment option for adolescents with depression and likely generates cost savings over 2 years,” said John F. Dickerson, PhD, of Kaiser Permanente Center for Health Research, Portland, Ore., and his associates

Rawpixel/Thinkstock

There’s a simple act you’ve done with all your patients that you’ve probably been doing incorrectly. Yes, that is rather a bold assertion, but I’ll bet no one ever taught you the proper way. It’s only recently, after having done it thousands of times, that I came to realize there is a better way to give a handshake.

Handshakes come both at the critical first moment and at the close of patient interactions. The first helps establish who you are as a doctor and reassures your patient that you’re both capable and trustworthy. At the end of the visit, it seals the agreement wherein they commit to take your advice (or at least try) and you commit to do whatever necessary to help them.

high-number/Thinkstock

A poorly executed handshake, or worse, none at all, can erode trust or convey a lack of ability on your part. It’s true that handshakes aren’t always appropriate: For certain patients or disease states, they would be unsuitable. For the majority of patient visits, however, they are key. Here are some secrets to a good handshake:
 

• As you’ve probably experienced, timing is critical. A handshake requires someone to anticipate your action and to coordinate perfectly with you. When you enter the room, move toward your patient and put your hand forward just as you approach your patient. Too early and you look like an awkward high schooler eager for a Justin Bieber autograph. Too late and you’ll take your patient by surprise. The best position is to have your left foot forward as you reach for their hand. This gives you stability and allows you to convey confidence.
• As you approach your patient, make eye contact. Just a second or two as you cross the room is perfect. Then glance down at their now outstretched hand and connect web to web. Your arm should be tucked in and move straight toward their hand. Swinging out to come back in is great when you’re getting your new NBA jersey from the basketball commissioner, but not for getting patients comfortable with you.
• The grip depends on the patient. For most adults, a firm squeeze with two arm pumps is just right. For the hard-charging, testosterone-replacing ex-Marine, you can reciprocate the extra-firm grasp – let him win the grip contest though, that’s what he wants. For the freezing-in-her-gown great grandmother, an extra long hold, sometimes even double handed, is fine, even appreciated.
• No matter how firm, it is important to convey your enthusiasm and ability to your patient. This is done with a gentle push. As you shake hands, lightly push their arm back into them. This subtle transfer of energy from you to them is a little known tip that will make your handshake much more effective. Never push them off balance or worse, pull them toward you. Your objective is to create trust; making them unsteady will make that impossible.
• Finally, let go after two pumps. If you feel them holding on, then stay until they release. For the majority of patients, that will be a just a couple seconds.

For patients I’ve never met, I often proffer my hand turned slightly upward for our first handshake. This subtle sign of submission shows I’m open and committed to them. For our closing handshake, I have my hand turned slightly downward so that my hand is slightly over theirs. This conveys that I’m confident in what I’ve said and done and that now I want them to uphold their part in our agreement.

I’ve been using the above technique for a few years now with success. It has helped with my patient satisfaction scores, and importantly, has helped me manage difficult patients for whom trust in our relationship is invaluable.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

There’s a simple act you’ve done with all your patients that you’ve probably been doing incorrectly. Yes, that is rather a bold assertion, but I’ll bet no one ever taught you the proper way. It’s only recently, after having done it thousands of times, that I came to realize there is a better way to give a handshake.

Handshakes come both at the critical first moment and at the close of patient interactions. The first helps establish who you are as a doctor and reassures your patient that you’re both capable and trustworthy. At the end of the visit, it seals the agreement wherein they commit to take your advice (or at least try) and you commit to do whatever necessary to help them.

high-number/Thinkstock

A poorly executed handshake, or worse, none at all, can erode trust or convey a lack of ability on your part. It’s true that handshakes aren’t always appropriate: For certain patients or disease states, they would be unsuitable. For the majority of patient visits, however, they are key. Here are some secrets to a good handshake:
 

• As you’ve probably experienced, timing is critical. A handshake requires someone to anticipate your action and to coordinate perfectly with you. When you enter the room, move toward your patient and put your hand forward just as you approach your patient. Too early and you look like an awkward high schooler eager for a Justin Bieber autograph. Too late and you’ll take your patient by surprise. The best position is to have your left foot forward as you reach for their hand. This gives you stability and allows you to convey confidence.
• As you approach your patient, make eye contact. Just a second or two as you cross the room is perfect. Then glance down at their now outstretched hand and connect web to web. Your arm should be tucked in and move straight toward their hand. Swinging out to come back in is great when you’re getting your new NBA jersey from the basketball commissioner, but not for getting patients comfortable with you.
• The grip depends on the patient. For most adults, a firm squeeze with two arm pumps is just right. For the hard-charging, testosterone-replacing ex-Marine, you can reciprocate the extra-firm grasp – let him win the grip contest though, that’s what he wants. For the freezing-in-her-gown great grandmother, an extra long hold, sometimes even double handed, is fine, even appreciated.
• No matter how firm, it is important to convey your enthusiasm and ability to your patient. This is done with a gentle push. As you shake hands, lightly push their arm back into them. This subtle transfer of energy from you to them is a little known tip that will make your handshake much more effective. Never push them off balance or worse, pull them toward you. Your objective is to create trust; making them unsteady will make that impossible.
• Finally, let go after two pumps. If you feel them holding on, then stay until they release. For the majority of patients, that will be a just a couple seconds.

For patients I’ve never met, I often proffer my hand turned slightly upward for our first handshake. This subtle sign of submission shows I’m open and committed to them. For our closing handshake, I have my hand turned slightly downward so that my hand is slightly over theirs. This conveys that I’m confident in what I’ve said and done and that now I want them to uphold their part in our agreement.

I’ve been using the above technique for a few years now with success. It has helped with my patient satisfaction scores, and importantly, has helped me manage difficult patients for whom trust in our relationship is invaluable.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

There’s a simple act you’ve done with all your patients that you’ve probably been doing incorrectly. Yes, that is rather a bold assertion, but I’ll bet no one ever taught you the proper way. It’s only recently, after having done it thousands of times, that I came to realize there is a better way to give a handshake.

Handshakes come both at the critical first moment and at the close of patient interactions. The first helps establish who you are as a doctor and reassures your patient that you’re both capable and trustworthy. At the end of the visit, it seals the agreement wherein they commit to take your advice (or at least try) and you commit to do whatever necessary to help them.

high-number/Thinkstock

A poorly executed handshake, or worse, none at all, can erode trust or convey a lack of ability on your part. It’s true that handshakes aren’t always appropriate: For certain patients or disease states, they would be unsuitable. For the majority of patient visits, however, they are key. Here are some secrets to a good handshake:
 

• As you’ve probably experienced, timing is critical. A handshake requires someone to anticipate your action and to coordinate perfectly with you. When you enter the room, move toward your patient and put your hand forward just as you approach your patient. Too early and you look like an awkward high schooler eager for a Justin Bieber autograph. Too late and you’ll take your patient by surprise. The best position is to have your left foot forward as you reach for their hand. This gives you stability and allows you to convey confidence.
• As you approach your patient, make eye contact. Just a second or two as you cross the room is perfect. Then glance down at their now outstretched hand and connect web to web. Your arm should be tucked in and move straight toward their hand. Swinging out to come back in is great when you’re getting your new NBA jersey from the basketball commissioner, but not for getting patients comfortable with you.
• The grip depends on the patient. For most adults, a firm squeeze with two arm pumps is just right. For the hard-charging, testosterone-replacing ex-Marine, you can reciprocate the extra-firm grasp – let him win the grip contest though, that’s what he wants. For the freezing-in-her-gown great grandmother, an extra long hold, sometimes even double handed, is fine, even appreciated.
• No matter how firm, it is important to convey your enthusiasm and ability to your patient. This is done with a gentle push. As you shake hands, lightly push their arm back into them. This subtle transfer of energy from you to them is a little known tip that will make your handshake much more effective. Never push them off balance or worse, pull them toward you. Your objective is to create trust; making them unsteady will make that impossible.
• Finally, let go after two pumps. If you feel them holding on, then stay until they release. For the majority of patients, that will be a just a couple seconds.

For patients I’ve never met, I often proffer my hand turned slightly upward for our first handshake. This subtle sign of submission shows I’m open and committed to them. For our closing handshake, I have my hand turned slightly downward so that my hand is slightly over theirs. This conveys that I’m confident in what I’ve said and done and that now I want them to uphold their part in our agreement.

I’ve been using the above technique for a few years now with success. It has helped with my patient satisfaction scores, and importantly, has helped me manage difficult patients for whom trust in our relationship is invaluable.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

A significant number of woman who delivered ahead of term and were already considered at risk for spontaneous preterm birth did not receive any sort of intervention to prevent the preterm birth, according to Yu Yang Feng and associates.

For the retrospective study, the researchers analyzed the medical records of 31 women who had been admitted to a primary, secondary, or tertiary prenatal care center and who had a history of spontaneous singleton preterm birth and/or cervical shortening before 24 weeks of gestation. Of the 23 women who were referred to a prenatal care center before reaching a gestational age of 24 weeks, only 13 were offered an intervention and only 12 received progesterone or cerclage as an intervention, while none received pessary. One of the 13 was offered and declined progesterone.

Of the 12 women who received an intervention before 24 weeks’ gestational age, 8 received progesterone, 2 received elective cerclage, and 2 received rescue cerclage. An additional woman who was referred to a prenatal care center after 24 weeks received progesterone, the only one in that group to receive an intervention.

Most of the women in the study were referred to a prenatal care center by their family physician, although two were referred by their midwife, one was referred by a nurse practitioner and fertility specialist, and three started their care with an obstetrician.

“Our findings that less than one in three women with a previous preterm birth or current short cervix received progesterone attest to the importance of improving knowledge translation with the latest evidence to encourage referral in time and use of this intervention for the prevention of preterm birth,” the study investigators concluded.

Find the full study in the Journal of Obstetrics and Gynaecology Canada (2018 Jan. doi: 10.1016/j.jogc.2017.08.036).

[email protected]

A significant number of woman who delivered ahead of term and were already considered at risk for spontaneous preterm birth did not receive any sort of intervention to prevent the preterm birth, according to Yu Yang Feng and associates.

For the retrospective study, the researchers analyzed the medical records of 31 women who had been admitted to a primary, secondary, or tertiary prenatal care center and who had a history of spontaneous singleton preterm birth and/or cervical shortening before 24 weeks of gestation. Of the 23 women who were referred to a prenatal care center before reaching a gestational age of 24 weeks, only 13 were offered an intervention and only 12 received progesterone or cerclage as an intervention, while none received pessary. One of the 13 was offered and declined progesterone.

Of the 12 women who received an intervention before 24 weeks’ gestational age, 8 received progesterone, 2 received elective cerclage, and 2 received rescue cerclage. An additional woman who was referred to a prenatal care center after 24 weeks received progesterone, the only one in that group to receive an intervention.

Most of the women in the study were referred to a prenatal care center by their family physician, although two were referred by their midwife, one was referred by a nurse practitioner and fertility specialist, and three started their care with an obstetrician.

“Our findings that less than one in three women with a previous preterm birth or current short cervix received progesterone attest to the importance of improving knowledge translation with the latest evidence to encourage referral in time and use of this intervention for the prevention of preterm birth,” the study investigators concluded.

Find the full study in the Journal of Obstetrics and Gynaecology Canada (2018 Jan. doi: 10.1016/j.jogc.2017.08.036).

[email protected]

A significant number of woman who delivered ahead of term and were already considered at risk for spontaneous preterm birth did not receive any sort of intervention to prevent the preterm birth, according to Yu Yang Feng and associates.

For the retrospective study, the researchers analyzed the medical records of 31 women who had been admitted to a primary, secondary, or tertiary prenatal care center and who had a history of spontaneous singleton preterm birth and/or cervical shortening before 24 weeks of gestation. Of the 23 women who were referred to a prenatal care center before reaching a gestational age of 24 weeks, only 13 were offered an intervention and only 12 received progesterone or cerclage as an intervention, while none received pessary. One of the 13 was offered and declined progesterone.

Of the 12 women who received an intervention before 24 weeks’ gestational age, 8 received progesterone, 2 received elective cerclage, and 2 received rescue cerclage. An additional woman who was referred to a prenatal care center after 24 weeks received progesterone, the only one in that group to receive an intervention.

Most of the women in the study were referred to a prenatal care center by their family physician, although two were referred by their midwife, one was referred by a nurse practitioner and fertility specialist, and three started their care with an obstetrician.

“Our findings that less than one in three women with a previous preterm birth or current short cervix received progesterone attest to the importance of improving knowledge translation with the latest evidence to encourage referral in time and use of this intervention for the prevention of preterm birth,” the study investigators concluded.

Find the full study in the Journal of Obstetrics and Gynaecology Canada (2018 Jan. doi: 10.1016/j.jogc.2017.08.036).

[email protected]

A topical retinoid plus topical benzoyl peroxide beats antibiotics as the first-line therapy for most patients with 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.

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.

[email protected]

SOURCE: Thiboutot DM et al. J Am Acad Dermatol. 2018 Feb. doi: 10.1016/j.jaad.2017.09.078.

A topical retinoid plus topical benzoyl peroxide beats antibiotics as the first-line therapy for most patients with 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.

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.

[email protected]

SOURCE: Thiboutot DM et al. J Am Acad Dermatol. 2018 Feb. doi: 10.1016/j.jaad.2017.09.078.

A topical retinoid plus topical benzoyl peroxide beats antibiotics as the first-line therapy for most patients with 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.

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.

[email protected]

SOURCE: Thiboutot DM et al. J Am Acad Dermatol. 2018 Feb. doi: 10.1016/j.jaad.2017.09.078.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.”

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.

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.

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.

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.”

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.

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.

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.

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.”

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.

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.

Mitchel L. Zoler/Frontline Medical News

[email protected]

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.

Mitchel L. Zoler/Frontline Medical News

[email protected]

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.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Zeidan A et al. ASH 2017 Abstract 640.

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.

[email protected]

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.

[email protected]

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.

[email protected]

SOURCE: Barner J et al. Am J Manag Care. 2017 Dec;23(19 Suppl):S363-70.

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.

Shidlovski/thinkstock

[email protected]

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.

Shidlovski/thinkstock

[email protected]

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.

Shidlovski/thinkstock

[email protected]

SOURCE: Mills JL et al. Hum Reprod. 2018 Jan 11. doi: 10.1093/humrep/dex379.