In the opinion of Andrea L. Zaenglein, MD, the initial assessment of patients who present with acne should include five quick steps.

olavs/Thinkstock

First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.

Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”

According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).

For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”

If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”

The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.

To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”

To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”

Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”

For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”

Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”

Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”

For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.

Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”

Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.

[email protected]

In the opinion of Andrea L. Zaenglein, MD, the initial assessment of patients who present with acne should include five quick steps.

olavs/Thinkstock

First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.

Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”

According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).

For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”

If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”

The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.

To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”

To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”

Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”

For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”

Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”

Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”

For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.

Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”

Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.

[email protected]

In the opinion of Andrea L. Zaenglein, MD, the initial assessment of patients who present with acne should include five quick steps.

olavs/Thinkstock

First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.

Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”

According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).

For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”

If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”

The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.

To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”

To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”

Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”

For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”

Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”

Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”

For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.

Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”

Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.

[email protected]

Nearly 40% of hundreds of opioid abusers at several emergency departments tested positive for stimulants, and they were more likely to be white than other users, a new study finds. Reflecting national trends, patients in the Midwest and West Coast regions were more likely to show signs of stimulant use.

Stimulant/opioid users were also “younger, with unstable housing, mostly unemployed, and reported high rates of recent incarcerations,” said substance use researcher and study lead author Marek Chawarski, PhD, of Yale University, New Haven, Conn. “They also reported higher rates of injection drug use during 1 month prior to the study admission and had higher rates of HCV infection. And higher proportions of amphetamine-type stimulant (ATS)–positive patients presented in the emergency departments (EDs) for an injury or with drug overdose.”

Dr. Chawarski, who presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence, said in an interview that the study is the first to analyze stimulant use in ED patients with opioid use disorder.

The researchers analyzed data for the period 2017-2019 from EDs in Baltimore, New York, Cincinnati, and Seattle. Out of 396 patients, 150 (38%) were positive for amphetamine-type stimulants.

Patients in the Midwest and West Coast were more likely to test positive (38%). The rates of stimulant use were 6% in Baltimore, 7% in New York, 32% in Cincinnati, and 80% in Seattle.

In general, stimulant use is higher in the Midwest and West Coast, said epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., in an interview. “This is due to a number of supply-side, historical, and cultural reasons. New England, Appalachia, and large urban centers on the East Coast are the historical hot spots for opioid use, while states west of the Mississippi River have lower rates of opioid overdose, but a much higher prevalence of ATS use and stimulant-related morbidity and mortality.”

Those who showed signs of stimulant use were more likely to be white (69%) vs. the nonusers (46%), and were more likely to have unstable housing (67% vs. 49%).

Those who used stimulants also were more likely to be suffering from an overdose (23% vs. 13%) and to report injecting drugs in the last month (79% vs. 47%). More had unstable housing (67% vs. 49%, P < .05 for all comparisons).

Dr. Chawarski said there are many reasons why users might use more than one kind of drug. For example, they may take one drug to “alleviate problems created by the use of one substance with taking another substance and multiple other reasons,” he said. “Polysubstance use can exacerbate social and medical harms, including overdose risk. It can pose greater treatment challenges, both for the patients and treatment providers, and often is more difficult to overcome.”

Links between opioid and stimulant use are not new. Last year, a study of 2,244 opioid-related overdose deaths in Massachusetts from 2014 to 2015 found that 36% of patients also showed signs of stimulant use. “Persons older than 24 years, nonrural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone,” the researchers reported (Drug Alcohol Depend. 2019 Jul 1;200:59-63).

Dr. Marshall said the study findings are not surprising. However, he said, they do indicate “ongoing, intentional consumption of opioids. The trends and characteristics we are seeing here suggests a large population of persons who are intentionally using both stimulants and opioids, many of whom are also injecting.”

He added that the study sample is probably higher risk than the general population since they’re presenting to the emergency department, so the findings might not reflect the use of stimulants in the general opioid-misusing population.

Dr. Marshall added that “there have been several instances in modern U.S. history during which increases in stimulant use follow a rise in opioid use, so the pattern we are seeing isn’t entirely surprising.”

“What we don’t know,” he added, “is the extent to which overdoses involving both an opioid and a stimulant are due to fentanyl contamination of the methamphetamine supply or intentional concurrent use – e.g., ‘speedballing’ or ‘goof balling’ – or some other pattern of polysubstance use, such as using an opioid to come down off a methamphetamine high.”

The National Institute on Drug Abuse funded the study. The study authors reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with two of the study coauthors.

Nearly 40% of hundreds of opioid abusers at several emergency departments tested positive for stimulants, and they were more likely to be white than other users, a new study finds. Reflecting national trends, patients in the Midwest and West Coast regions were more likely to show signs of stimulant use.

Stimulant/opioid users were also “younger, with unstable housing, mostly unemployed, and reported high rates of recent incarcerations,” said substance use researcher and study lead author Marek Chawarski, PhD, of Yale University, New Haven, Conn. “They also reported higher rates of injection drug use during 1 month prior to the study admission and had higher rates of HCV infection. And higher proportions of amphetamine-type stimulant (ATS)–positive patients presented in the emergency departments (EDs) for an injury or with drug overdose.”

Dr. Chawarski, who presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence, said in an interview that the study is the first to analyze stimulant use in ED patients with opioid use disorder.

The researchers analyzed data for the period 2017-2019 from EDs in Baltimore, New York, Cincinnati, and Seattle. Out of 396 patients, 150 (38%) were positive for amphetamine-type stimulants.

Patients in the Midwest and West Coast were more likely to test positive (38%). The rates of stimulant use were 6% in Baltimore, 7% in New York, 32% in Cincinnati, and 80% in Seattle.

In general, stimulant use is higher in the Midwest and West Coast, said epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., in an interview. “This is due to a number of supply-side, historical, and cultural reasons. New England, Appalachia, and large urban centers on the East Coast are the historical hot spots for opioid use, while states west of the Mississippi River have lower rates of opioid overdose, but a much higher prevalence of ATS use and stimulant-related morbidity and mortality.”

Those who showed signs of stimulant use were more likely to be white (69%) vs. the nonusers (46%), and were more likely to have unstable housing (67% vs. 49%).

Those who used stimulants also were more likely to be suffering from an overdose (23% vs. 13%) and to report injecting drugs in the last month (79% vs. 47%). More had unstable housing (67% vs. 49%, P < .05 for all comparisons).

Dr. Chawarski said there are many reasons why users might use more than one kind of drug. For example, they may take one drug to “alleviate problems created by the use of one substance with taking another substance and multiple other reasons,” he said. “Polysubstance use can exacerbate social and medical harms, including overdose risk. It can pose greater treatment challenges, both for the patients and treatment providers, and often is more difficult to overcome.”

Links between opioid and stimulant use are not new. Last year, a study of 2,244 opioid-related overdose deaths in Massachusetts from 2014 to 2015 found that 36% of patients also showed signs of stimulant use. “Persons older than 24 years, nonrural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone,” the researchers reported (Drug Alcohol Depend. 2019 Jul 1;200:59-63).

Dr. Marshall said the study findings are not surprising. However, he said, they do indicate “ongoing, intentional consumption of opioids. The trends and characteristics we are seeing here suggests a large population of persons who are intentionally using both stimulants and opioids, many of whom are also injecting.”

He added that the study sample is probably higher risk than the general population since they’re presenting to the emergency department, so the findings might not reflect the use of stimulants in the general opioid-misusing population.

Dr. Marshall added that “there have been several instances in modern U.S. history during which increases in stimulant use follow a rise in opioid use, so the pattern we are seeing isn’t entirely surprising.”

“What we don’t know,” he added, “is the extent to which overdoses involving both an opioid and a stimulant are due to fentanyl contamination of the methamphetamine supply or intentional concurrent use – e.g., ‘speedballing’ or ‘goof balling’ – or some other pattern of polysubstance use, such as using an opioid to come down off a methamphetamine high.”

The National Institute on Drug Abuse funded the study. The study authors reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with two of the study coauthors.

Nearly 40% of hundreds of opioid abusers at several emergency departments tested positive for stimulants, and they were more likely to be white than other users, a new study finds. Reflecting national trends, patients in the Midwest and West Coast regions were more likely to show signs of stimulant use.

Stimulant/opioid users were also “younger, with unstable housing, mostly unemployed, and reported high rates of recent incarcerations,” said substance use researcher and study lead author Marek Chawarski, PhD, of Yale University, New Haven, Conn. “They also reported higher rates of injection drug use during 1 month prior to the study admission and had higher rates of HCV infection. And higher proportions of amphetamine-type stimulant (ATS)–positive patients presented in the emergency departments (EDs) for an injury or with drug overdose.”

Dr. Chawarski, who presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence, said in an interview that the study is the first to analyze stimulant use in ED patients with opioid use disorder.

The researchers analyzed data for the period 2017-2019 from EDs in Baltimore, New York, Cincinnati, and Seattle. Out of 396 patients, 150 (38%) were positive for amphetamine-type stimulants.

Patients in the Midwest and West Coast were more likely to test positive (38%). The rates of stimulant use were 6% in Baltimore, 7% in New York, 32% in Cincinnati, and 80% in Seattle.

In general, stimulant use is higher in the Midwest and West Coast, said epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., in an interview. “This is due to a number of supply-side, historical, and cultural reasons. New England, Appalachia, and large urban centers on the East Coast are the historical hot spots for opioid use, while states west of the Mississippi River have lower rates of opioid overdose, but a much higher prevalence of ATS use and stimulant-related morbidity and mortality.”

Those who showed signs of stimulant use were more likely to be white (69%) vs. the nonusers (46%), and were more likely to have unstable housing (67% vs. 49%).

Those who used stimulants also were more likely to be suffering from an overdose (23% vs. 13%) and to report injecting drugs in the last month (79% vs. 47%). More had unstable housing (67% vs. 49%, P < .05 for all comparisons).

Dr. Chawarski said there are many reasons why users might use more than one kind of drug. For example, they may take one drug to “alleviate problems created by the use of one substance with taking another substance and multiple other reasons,” he said. “Polysubstance use can exacerbate social and medical harms, including overdose risk. It can pose greater treatment challenges, both for the patients and treatment providers, and often is more difficult to overcome.”

Links between opioid and stimulant use are not new. Last year, a study of 2,244 opioid-related overdose deaths in Massachusetts from 2014 to 2015 found that 36% of patients also showed signs of stimulant use. “Persons older than 24 years, nonrural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone,” the researchers reported (Drug Alcohol Depend. 2019 Jul 1;200:59-63).

Dr. Marshall said the study findings are not surprising. However, he said, they do indicate “ongoing, intentional consumption of opioids. The trends and characteristics we are seeing here suggests a large population of persons who are intentionally using both stimulants and opioids, many of whom are also injecting.”

He added that the study sample is probably higher risk than the general population since they’re presenting to the emergency department, so the findings might not reflect the use of stimulants in the general opioid-misusing population.

Dr. Marshall added that “there have been several instances in modern U.S. history during which increases in stimulant use follow a rise in opioid use, so the pattern we are seeing isn’t entirely surprising.”

“What we don’t know,” he added, “is the extent to which overdoses involving both an opioid and a stimulant are due to fentanyl contamination of the methamphetamine supply or intentional concurrent use – e.g., ‘speedballing’ or ‘goof balling’ – or some other pattern of polysubstance use, such as using an opioid to come down off a methamphetamine high.”

The National Institute on Drug Abuse funded the study. The study authors reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with two of the study coauthors.

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

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

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

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

Treating hypertension with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) was associated with a reduced risk for colorectal cancer, according to findings from a large retrospective study.

However, another study reported just over a year ago suggested that ACE inhibitors, but not ARBs, are associated with an increased risk for lung cancer. An expert approached for comment emphasized that both studies are observational, and, as such, they only show an association, not causation.

In this latest study, published online July 6 in the journal Hypertension, the use of ACE inhibitors/ARBs was associated with a 22% lower risk for colorectal cancer developing within 3 years after a negative baseline colonoscopy.

This is the largest study to date, with a cohort of more than 185,000 patients, to suggest a significant protective effect for these two common antihypertensive medications, the authors note. The risk of developing colorectal cancer decreased with longer duration of ACE inhibitor/ARB use, with a 5% reduction in adjusted hazard ratio risk for each year of use. However, this effect was limited to patients who had negative colonoscopies within a 3-year period and did not extend beyond that point.

Lead author Wai K. Leung, MD, clinical professor of medicine at the University of Hong Kong, explained that they are not advising patients to take ACE inhibitors simply to prevent cancer. “Unlike aspirin and statins, the potential chemopreventive role of ACE inhibitors on cancer has never been established,” he said in an interview. “The study findings may favor the use of ACE inhibitors in the treatment of hypertension, over many other antihypertensives, in some patients for preventing colorectal cancer.”

Increased or reduced risk?

There has been considerable debate about the potential carcinogenic effects of ACE inhibitors and ARBs, and the relationship with “various solid organ cancer risks have been unsettled,” the authors note. Studies have produced conflicting results – showing no overall cancer risk and a modestly increased overall cancer risk – associated with these agents.

A recent study reported that ACE inhibitors, as compared with ARBs, increased risk for lung cancer by 14%. The risk for lung cancer increased by 22% among those using ACE inhibitors for 5 years, and the risk peaked at 31% for patients who took ACE inhibitors for 10 years or longer.

The lead author of that lung cancer study, Laurent Azoulay, PhD, of McGill University in Montreal, offered some thoughts on the seemingly conflicting data now being reported showing a reduction in the risk of colorectal cancer.

“In a nutshell, this study has important methodologic issues that can explain the observed findings,” he said in an interview.

Dr. Azoulay pointed out that, in the univariate model, the use of ACE inhibitors/ARBs was associated with a 26% increased risk of colorectal cancer. “It is only after propensity score adjustment that the effect estimate reversed in the protective direction,” he pointed out. “However, the variables included in the propensity score model were measured in the same time window as the exposure, which can lead to an overadjustment bias and generate spurious findings.”

Another issue is that the study period did not begin at the time of the exposure, but rather at a distant point after treatment initiation – in this case, colorectal cancer screening. “As such, the authors excluded patients who were previously diagnosed with colorectal cancer prior to that point, which likely included patients exposed to ACE inhibitors/ARBs,” he said. “This approach can lead to the inclusion of the ‘survivors’ for whom the risk of developing colorectal cancer is lower.

“But certainly,” Dr. Azoulay added, “this possible association should be investigated using methodologically sound approaches.”

Take-home message for physicians

Another expert emphasized the observational nature of both studies. Raymond Townsend, MD, director of the Hypertension Program and a professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, said: “First and foremost, these are observational studies and cannot make inference about causality; they can only show associations.”

He pointed out that, sometimes, associations are truly present, whereas at other times, there is bias or confounding that cannot be controlled for statistically because it is “unknown.” That said, the size of this latest study is a plus, and there is a reasonable follow-up period.

“The take-home [message] for practitioners is that there may be a benefit in keeping older people on ACE inhibitors on the likelihood of developing colorectal cancer if your last colonoscopy was negative,” Dr. Townsend, who was not involved in the study, said in an interview.

But there are some questions that remain unanswered regarding characteristics of the cohort, Dr. Townsend noted. “Who were the people having the colonoscopy in the first place? Were they a group at higher risk? Why were some on an ACE inhibitors/ARBs and many others not?” 

There are other conclusions that clinicians can glean from this. “Make a choice of treatment for a patient based on your best estimate of what will lower their blood pressure and prevent hypertension-mediated organ damage,” said Dr. Townsend, who is also an American Heart Association volunteer expert. “Keep in mind that patients hear about these studies and read unreviewed blogs on the web and so have questions.”

He emphasized that it always comes back to two things. “One is that every treatment decision is inherently a risk-benefit scenario,” he said. “And second is that most of our patients are adults, and if they choose to not be treated for their hypertension despite our best advice and reasoning with them, relinquish control and let them proceed as they wish, offering to renegotiate in the future when and if they reconsider.”

Study details

In the latest study, Dr. Leung and colleagues conducted a retrospective cohort study and used data from an electronic health care database of the Hong Kong Hospital Authority. A total of 187,897 individuals aged 40 years and older had undergone colonoscopy between 2005 and 2013 with a negative result and were included in the analysis.

The study’s primary outcome was colorectal cancer that was diagnosed between 6 and 36 months after undergoing colonoscopy, and the median age at colonoscopy was 60.6 years. Within this population, 30,856 patients (16.4%) used ACE inhibitors/ARBs.

Between 6 months and 3 years after undergoing colonoscopy, 854 cases of colorectal cancer were diagnosed, with an incidence rate of 15.2 per 10,000 person-years. The median time between colonoscopy and diagnosis was 1.2 years.

ACE inhibitor/ARB users had a median duration of 3.3 years of use within the 5-year period before their colonoscopy. Within this group, there were 169 (0.55%) cases of colorectal cancer. On univariate analysis, the crude hazard ratio (HR) of colorectal cancer and ACE inhibitor/ARB use was 1.26 (P = .008), but on propensity score regression adjustment, the adjusted HR became 0.78.

The propensity score absolute reduction in risk for users was 3.2 per 10,000 person-years versus nonusers, and stratification by subsite showed an HR of 0.77 for distal cancers and 0.83 for proximal cancers.

In a subgroup analysis, the benefits of ACE inhibitors and ARBs were seen in patients aged 55 years or older (adjusted HR, 0.79) and in those with a history of colonic polyps (adjusted HR, 0.71).

The authors also assessed if there was an association between these medications and other types of cancer. On univariate analysis, usage was associated with an increased risk of lung and prostate cancer but lower risk of breast cancer. But after propensity score regression adjustment, the associations were no longer there.

The study was funded by the Health and Medical Research Fund of the Hong Kong SAR Government. Dr. Leung has received honorarium for attending advisory board meetings of AbbVie, Takeda, and Abbott Laboratories; coauthor Esther W. Chan has received funding support from Pfizer, Bristol-Myers Squibb, Bayer, Takeda, Janssen (a division of Johnson & Johnson); Research Grants Council of Hong Kong; Narcotics Division, Security Bureau; and the National Natural Science Foundation of China, all for work unrelated to the current study. None of the other authors have disclosed relevant financial relationships. Dr. Azoulay has disclosed no relevant financial relationships. Dr. Townsend is employed by Penn Medicine.

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

Here are the stories our MDedge editors across specialties think you need to know about today:

Lifestyle choices may reduce breast cancer risk regardless of genetics

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” said William Gradishar, MD, who was not invovled with the study. Read more.

Primary care practices may lose $68K per physician this year

Primary care practices stand to lose almost $68,000 per full-time physician this year as COVID-19 causes care delays and cancellations, researchers estimate. And while some outpatient care has started to rebound to near baseline appointment levels, other ambulatory specialties remain dramatically down from prepandemic rates.

Dermatology and rheumatology visits have recovered, but some specialties have cumulative deficits that are particularly concerning. For example, pediatric visits were down by 47% in the 3 months since March 15, and pulmonology visits were down 45% in that time.

This primary care estimate is without a potential second wave of COVID-19, noted Sanjay Basu, MD, director of research and population health at Collective Health in San Francisco, and colleagues.

“We expect ongoing turbulent times, so having a prospective payment could unleash the capacity for primary care practices to be creative in the way they care for their patients,” Daniel Horn, MD, director of population health and quality at Massachusetts General Hospital in Boston, said in an interview. Read more.

Big pharma sues to block Minnesota insulin affordability law

The Pharmaceutical Research and Manufacturers Association (PhRMA) is suing the state of Minnesota in an attempt to overturn a law that requires insulin makers to provide an emergency supply to individuals free of charge.

In the July 1 filing, PhRMA’s attorneys said the law is unconstitutional. It “order[s] pharmaceutical manufacturers to give insulin to state residents, on the state’s prescribed terms, at no charge to the recipients and without compensating the manufacturers in any way.”

The state has estimated that as many as 30,000 Minnesotans would be eligible for free insulin in the first year of the program. The drugmakers strenuously objected, noting that would mean they would “be compelled to provide 173,800 monthly supplies of free insulin” just in the first year.

“There is nothing in the U.S. Constitution that prevents states from saving the lives of its citizens who are in imminent danger,” said Mayo Clinic hematologist S. Vincent Rajkumar, MD. “The only motives for this lawsuit in my opinion are greed and the worry that other states may also choose to put lives of patients ahead of pharma profits.” Read more.

Despite guidelines, kids get opioids & steroids for pneumonia, sinusitis

A significant percentage of children receive opioids and systemic corticosteroids for pneumonia and sinusitis despite guidelines, according to an analysis of 2016 Medicaid data from South Carolina.

Prescriptions for these drugs were more likely after visits to EDs than after ambulatory visits, researchers reported in Pediatrics.

“Each of the 828 opioid and 2,737 systemic steroid prescriptions in the data set represent a potentially inappropriate prescription,” wrote Karina G. Phang, MD, MPH, of Geisinger Medical Center in Danville, Pa., and colleagues. “These rates appear excessive given that the use of these medications is not supported by available research or recommended in national guidelines.” Read more.

Study supports changing classification of RCC

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Lifestyle choices may reduce breast cancer risk regardless of genetics

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” said William Gradishar, MD, who was not invovled with the study. Read more.

Primary care practices may lose $68K per physician this year

Primary care practices stand to lose almost $68,000 per full-time physician this year as COVID-19 causes care delays and cancellations, researchers estimate. And while some outpatient care has started to rebound to near baseline appointment levels, other ambulatory specialties remain dramatically down from prepandemic rates.

Dermatology and rheumatology visits have recovered, but some specialties have cumulative deficits that are particularly concerning. For example, pediatric visits were down by 47% in the 3 months since March 15, and pulmonology visits were down 45% in that time.

This primary care estimate is without a potential second wave of COVID-19, noted Sanjay Basu, MD, director of research and population health at Collective Health in San Francisco, and colleagues.

“We expect ongoing turbulent times, so having a prospective payment could unleash the capacity for primary care practices to be creative in the way they care for their patients,” Daniel Horn, MD, director of population health and quality at Massachusetts General Hospital in Boston, said in an interview. Read more.

Big pharma sues to block Minnesota insulin affordability law

The Pharmaceutical Research and Manufacturers Association (PhRMA) is suing the state of Minnesota in an attempt to overturn a law that requires insulin makers to provide an emergency supply to individuals free of charge.

In the July 1 filing, PhRMA’s attorneys said the law is unconstitutional. It “order[s] pharmaceutical manufacturers to give insulin to state residents, on the state’s prescribed terms, at no charge to the recipients and without compensating the manufacturers in any way.”

The state has estimated that as many as 30,000 Minnesotans would be eligible for free insulin in the first year of the program. The drugmakers strenuously objected, noting that would mean they would “be compelled to provide 173,800 monthly supplies of free insulin” just in the first year.

“There is nothing in the U.S. Constitution that prevents states from saving the lives of its citizens who are in imminent danger,” said Mayo Clinic hematologist S. Vincent Rajkumar, MD. “The only motives for this lawsuit in my opinion are greed and the worry that other states may also choose to put lives of patients ahead of pharma profits.” Read more.

Despite guidelines, kids get opioids & steroids for pneumonia, sinusitis

A significant percentage of children receive opioids and systemic corticosteroids for pneumonia and sinusitis despite guidelines, according to an analysis of 2016 Medicaid data from South Carolina.

Prescriptions for these drugs were more likely after visits to EDs than after ambulatory visits, researchers reported in Pediatrics.

“Each of the 828 opioid and 2,737 systemic steroid prescriptions in the data set represent a potentially inappropriate prescription,” wrote Karina G. Phang, MD, MPH, of Geisinger Medical Center in Danville, Pa., and colleagues. “These rates appear excessive given that the use of these medications is not supported by available research or recommended in national guidelines.” Read more.

Study supports changing classification of RCC

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Lifestyle choices may reduce breast cancer risk regardless of genetics

A “favorable” lifestyle was associated with a reduced risk of breast cancer even among women at high genetic risk for the disease in a study of more than 90,000 women, researchers reported.

The findings suggest that, regardless of genetic risk, women may be able to reduce their risk of developing breast cancer by getting adequate levels of exercise; maintaining a healthy weight; and limiting or eliminating use of alcohol, oral contraceptives, and hormone replacement therapy.

“These data should empower patients that they can impact on their overall health and reduce the risk of developing breast cancer,” said William Gradishar, MD, who was not invovled with the study. Read more.

Primary care practices may lose $68K per physician this year

Primary care practices stand to lose almost $68,000 per full-time physician this year as COVID-19 causes care delays and cancellations, researchers estimate. And while some outpatient care has started to rebound to near baseline appointment levels, other ambulatory specialties remain dramatically down from prepandemic rates.

Dermatology and rheumatology visits have recovered, but some specialties have cumulative deficits that are particularly concerning. For example, pediatric visits were down by 47% in the 3 months since March 15, and pulmonology visits were down 45% in that time.

This primary care estimate is without a potential second wave of COVID-19, noted Sanjay Basu, MD, director of research and population health at Collective Health in San Francisco, and colleagues.

“We expect ongoing turbulent times, so having a prospective payment could unleash the capacity for primary care practices to be creative in the way they care for their patients,” Daniel Horn, MD, director of population health and quality at Massachusetts General Hospital in Boston, said in an interview. Read more.

Big pharma sues to block Minnesota insulin affordability law

The Pharmaceutical Research and Manufacturers Association (PhRMA) is suing the state of Minnesota in an attempt to overturn a law that requires insulin makers to provide an emergency supply to individuals free of charge.

In the July 1 filing, PhRMA’s attorneys said the law is unconstitutional. It “order[s] pharmaceutical manufacturers to give insulin to state residents, on the state’s prescribed terms, at no charge to the recipients and without compensating the manufacturers in any way.”

The state has estimated that as many as 30,000 Minnesotans would be eligible for free insulin in the first year of the program. The drugmakers strenuously objected, noting that would mean they would “be compelled to provide 173,800 monthly supplies of free insulin” just in the first year.

“There is nothing in the U.S. Constitution that prevents states from saving the lives of its citizens who are in imminent danger,” said Mayo Clinic hematologist S. Vincent Rajkumar, MD. “The only motives for this lawsuit in my opinion are greed and the worry that other states may also choose to put lives of patients ahead of pharma profits.” Read more.

Despite guidelines, kids get opioids & steroids for pneumonia, sinusitis

A significant percentage of children receive opioids and systemic corticosteroids for pneumonia and sinusitis despite guidelines, according to an analysis of 2016 Medicaid data from South Carolina.

Prescriptions for these drugs were more likely after visits to EDs than after ambulatory visits, researchers reported in Pediatrics.

“Each of the 828 opioid and 2,737 systemic steroid prescriptions in the data set represent a potentially inappropriate prescription,” wrote Karina G. Phang, MD, MPH, of Geisinger Medical Center in Danville, Pa., and colleagues. “These rates appear excessive given that the use of these medications is not supported by available research or recommended in national guidelines.” Read more.

Study supports changing classification of RCC

The definition of stage IV renal cell carcinoma (RCC) should be expanded to include lymph node–positive stage III disease, according to a population-level cohort study published in Cancer.

While patients with lymph node–negative stage III disease had superior overall survival at 5 years, survival rates were similar between patients with node–positive stage III disease and stage IV disease. This supports reclassifying stage III node-positive RCC to stage IV, according to researchers.

“Prior institutional studies have indicated that, among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease,” wrote Arnav Srivastava, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and colleagues. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Patients with COVID-19 may be at increased risk of acute ischemic stroke compared with patients with influenza, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.

While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
 

An increased risk of stroke

The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.

Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.

The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).

This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”

The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).

In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).

The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
 

COVID or conventional risk factors?

Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”

Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).

He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”

SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.

Patients with COVID-19 may be at increased risk of acute ischemic stroke compared with patients with influenza, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.

While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
 

An increased risk of stroke

The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.

Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.

The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).

This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”

The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).

In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).

The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
 

COVID or conventional risk factors?

Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”

Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).

He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”

SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.

Patients with COVID-19 may be at increased risk of acute ischemic stroke compared with patients with influenza, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.

While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
 

An increased risk of stroke

The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.

Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.

The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).

This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”

The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).

In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).

The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
 

COVID or conventional risk factors?

Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”

Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).

He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”

SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.

Background: Alterations to the coagulation cascade put cirrhotic patients at higher risk for bleeding and thrombotic complications.

As such, pharmacologic VTE prophylaxis is often underutilized in patients admitted with cirrhosis; for patients requiring therapeutic anticoagulation, direct oral anticoagulants are safe in stable patients with mild cirrhosis, but should be avoided in Child-Pugh B and C patients.

Bottom line: Cirrhotic patients do not require routine correction of coagulopathy prior to low-risk procedures.

Citation: O’Leary JG et al. AGA Clinical Practice Update: Coagulation in cirrhosis. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.

Dr. Lublin is a hospitalist at the University of Colorado at Denver, Aurora.

Background: Alterations to the coagulation cascade put cirrhotic patients at higher risk for bleeding and thrombotic complications.

As such, pharmacologic VTE prophylaxis is often underutilized in patients admitted with cirrhosis; for patients requiring therapeutic anticoagulation, direct oral anticoagulants are safe in stable patients with mild cirrhosis, but should be avoided in Child-Pugh B and C patients.

Bottom line: Cirrhotic patients do not require routine correction of coagulopathy prior to low-risk procedures.

Citation: O’Leary JG et al. AGA Clinical Practice Update: Coagulation in cirrhosis. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.

Dr. Lublin is a hospitalist at the University of Colorado at Denver, Aurora.

Background: Alterations to the coagulation cascade put cirrhotic patients at higher risk for bleeding and thrombotic complications.

As such, pharmacologic VTE prophylaxis is often underutilized in patients admitted with cirrhosis; for patients requiring therapeutic anticoagulation, direct oral anticoagulants are safe in stable patients with mild cirrhosis, but should be avoided in Child-Pugh B and C patients.

Bottom line: Cirrhotic patients do not require routine correction of coagulopathy prior to low-risk procedures.

Citation: O’Leary JG et al. AGA Clinical Practice Update: Coagulation in cirrhosis. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.070.

Dr. Lublin is a hospitalist at the University of Colorado at Denver, Aurora.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

The Society of Hospital Medicine officially welcomed Eric E. Howell, MD, MHM, as chief executive officer on July 1, 2020. Dr. Howell reports to the Society of Hospital Medicine board of directors and is tasked with ensuring that SHM continues to serve the evolving needs and interests of its members while overseeing the organization’s strategic direction.

“The SHM board of directors is excited to work with Dr. Howell to navigate the future of SHM and of the hospital medicine specialty,” said Danielle Scheurer, MD, MSCR, SFHM, SHM president and chair of the CEO Search Committee. “With his extensive knowledge of the health care landscape and of SHM, Dr. Howell embodies the society’s dedication to empowering hospitalists to be positive change agents in their institutions and in the health care system as a whole.”

Prior to his current role, Dr. Howell served as chief operating officer of SHM for 2 years; in that role, he led senior management’s planning and defined organizational goals to drive growth. As the senior physician adviser to SHM’s Center for Quality Improvement for 5 years, he consulted for the society’s arm that conducts quality improvement programs for hospitalist teams. In addition to being a past president of SHM’s board of directors, he is the course director for the SHM Leadership Academies.

“Now more than ever, SHM has an opportunity to superserve hospitalists and the patients they serve, and I couldn’t be more excited to lead the society into its next chapter,” Dr. Howell said. “Supported by a dedicated member base and innovative staff, I am confident that SHM will continue on its successful path forward and will provide its members with the products, services, and tools that hospitalists need to improve patient care and adapt to the constantly evolving environment.”

In addition to serving in various capacities at SHM, Dr. Howell has served as a professor of medicine in the department of medicine at Johns Hopkins University, Baltimore. He has held multiple titles within the Johns Hopkins medical institutions, including chief of the division of hospital medicine at Johns Hopkins Bayview, section chief of hospital medicine for Johns Hopkins Community Physicians, deputy director of hospital operations for the department of medicine at Johns Hopkins Bayview Medical Center, and chief medical officer of operations at Johns Hopkins Bayview. Dr. Howell joined the Johns Hopkins Bayview hospitalist program in 2000, began the Howard County (Md.) General Hospital hospitalist program in 2010, and oversaw nearly 200 physicians and clinical staff providing patient care in three hospitals. Along with his role as SHM CEO, he will remain a member of the adjunct faculty at Johns Hopkins University.

More recently, Dr. Howell served as chief medical officer for the Baltimore Convention Center Field Hospital, a fully functional, 250-bed hospital created to care for patients in the Baltimore metropolitan area who were suffering from complications from COVID-19.

Dr. Howell received his electrical engineering degree from the University of Maryland, College Park, which has proven instrumental in his mastery of managing and implementing change in the hospital. His research has focused on the relationship between the emergency department and medicine floors, improving communication, throughput and patient outcomes.

The nationwide search process that led to Dr. Howell’s appointment was led by a CEO Search Committee, which included members of the SHM board of directors and was assisted by the executive search firm Spencer Stuart.

Dr. Howell succeeds Laurence Wellikson, MD, MHM, who helped in founding the Society of Hospital Medicine, its first and only CEO since 2000 prior to Dr. Howell’s appointment.

The Society of Hospital Medicine officially welcomed Eric E. Howell, MD, MHM, as chief executive officer on July 1, 2020. Dr. Howell reports to the Society of Hospital Medicine board of directors and is tasked with ensuring that SHM continues to serve the evolving needs and interests of its members while overseeing the organization’s strategic direction.

“The SHM board of directors is excited to work with Dr. Howell to navigate the future of SHM and of the hospital medicine specialty,” said Danielle Scheurer, MD, MSCR, SFHM, SHM president and chair of the CEO Search Committee. “With his extensive knowledge of the health care landscape and of SHM, Dr. Howell embodies the society’s dedication to empowering hospitalists to be positive change agents in their institutions and in the health care system as a whole.”

Prior to his current role, Dr. Howell served as chief operating officer of SHM for 2 years; in that role, he led senior management’s planning and defined organizational goals to drive growth. As the senior physician adviser to SHM’s Center for Quality Improvement for 5 years, he consulted for the society’s arm that conducts quality improvement programs for hospitalist teams. In addition to being a past president of SHM’s board of directors, he is the course director for the SHM Leadership Academies.

“Now more than ever, SHM has an opportunity to superserve hospitalists and the patients they serve, and I couldn’t be more excited to lead the society into its next chapter,” Dr. Howell said. “Supported by a dedicated member base and innovative staff, I am confident that SHM will continue on its successful path forward and will provide its members with the products, services, and tools that hospitalists need to improve patient care and adapt to the constantly evolving environment.”

In addition to serving in various capacities at SHM, Dr. Howell has served as a professor of medicine in the department of medicine at Johns Hopkins University, Baltimore. He has held multiple titles within the Johns Hopkins medical institutions, including chief of the division of hospital medicine at Johns Hopkins Bayview, section chief of hospital medicine for Johns Hopkins Community Physicians, deputy director of hospital operations for the department of medicine at Johns Hopkins Bayview Medical Center, and chief medical officer of operations at Johns Hopkins Bayview. Dr. Howell joined the Johns Hopkins Bayview hospitalist program in 2000, began the Howard County (Md.) General Hospital hospitalist program in 2010, and oversaw nearly 200 physicians and clinical staff providing patient care in three hospitals. Along with his role as SHM CEO, he will remain a member of the adjunct faculty at Johns Hopkins University.

More recently, Dr. Howell served as chief medical officer for the Baltimore Convention Center Field Hospital, a fully functional, 250-bed hospital created to care for patients in the Baltimore metropolitan area who were suffering from complications from COVID-19.

Dr. Howell received his electrical engineering degree from the University of Maryland, College Park, which has proven instrumental in his mastery of managing and implementing change in the hospital. His research has focused on the relationship between the emergency department and medicine floors, improving communication, throughput and patient outcomes.

The nationwide search process that led to Dr. Howell’s appointment was led by a CEO Search Committee, which included members of the SHM board of directors and was assisted by the executive search firm Spencer Stuart.

Dr. Howell succeeds Laurence Wellikson, MD, MHM, who helped in founding the Society of Hospital Medicine, its first and only CEO since 2000 prior to Dr. Howell’s appointment.

The Society of Hospital Medicine officially welcomed Eric E. Howell, MD, MHM, as chief executive officer on July 1, 2020. Dr. Howell reports to the Society of Hospital Medicine board of directors and is tasked with ensuring that SHM continues to serve the evolving needs and interests of its members while overseeing the organization’s strategic direction.

“The SHM board of directors is excited to work with Dr. Howell to navigate the future of SHM and of the hospital medicine specialty,” said Danielle Scheurer, MD, MSCR, SFHM, SHM president and chair of the CEO Search Committee. “With his extensive knowledge of the health care landscape and of SHM, Dr. Howell embodies the society’s dedication to empowering hospitalists to be positive change agents in their institutions and in the health care system as a whole.”

Prior to his current role, Dr. Howell served as chief operating officer of SHM for 2 years; in that role, he led senior management’s planning and defined organizational goals to drive growth. As the senior physician adviser to SHM’s Center for Quality Improvement for 5 years, he consulted for the society’s arm that conducts quality improvement programs for hospitalist teams. In addition to being a past president of SHM’s board of directors, he is the course director for the SHM Leadership Academies.

“Now more than ever, SHM has an opportunity to superserve hospitalists and the patients they serve, and I couldn’t be more excited to lead the society into its next chapter,” Dr. Howell said. “Supported by a dedicated member base and innovative staff, I am confident that SHM will continue on its successful path forward and will provide its members with the products, services, and tools that hospitalists need to improve patient care and adapt to the constantly evolving environment.”

In addition to serving in various capacities at SHM, Dr. Howell has served as a professor of medicine in the department of medicine at Johns Hopkins University, Baltimore. He has held multiple titles within the Johns Hopkins medical institutions, including chief of the division of hospital medicine at Johns Hopkins Bayview, section chief of hospital medicine for Johns Hopkins Community Physicians, deputy director of hospital operations for the department of medicine at Johns Hopkins Bayview Medical Center, and chief medical officer of operations at Johns Hopkins Bayview. Dr. Howell joined the Johns Hopkins Bayview hospitalist program in 2000, began the Howard County (Md.) General Hospital hospitalist program in 2010, and oversaw nearly 200 physicians and clinical staff providing patient care in three hospitals. Along with his role as SHM CEO, he will remain a member of the adjunct faculty at Johns Hopkins University.

More recently, Dr. Howell served as chief medical officer for the Baltimore Convention Center Field Hospital, a fully functional, 250-bed hospital created to care for patients in the Baltimore metropolitan area who were suffering from complications from COVID-19.

Dr. Howell received his electrical engineering degree from the University of Maryland, College Park, which has proven instrumental in his mastery of managing and implementing change in the hospital. His research has focused on the relationship between the emergency department and medicine floors, improving communication, throughput and patient outcomes.

The nationwide search process that led to Dr. Howell’s appointment was led by a CEO Search Committee, which included members of the SHM board of directors and was assisted by the executive search firm Spencer Stuart.

Dr. Howell succeeds Laurence Wellikson, MD, MHM, who helped in founding the Society of Hospital Medicine, its first and only CEO since 2000 prior to Dr. Howell’s appointment.

CASE Patient questions need for postpartum BP check

Ms. P presents at 28 weeks’ gestation with superimposed preeclampsia. She receives antenatal corticosteroids and titration of her nifedipine, but she is delivered at 29 weeks because of worsening fetal status. Her physician recommends a blood pressure (BP) visit in the office at 7 days postpartum.

She asks, “But can’t I just call you with the BP reading? And what do I do in the meantime?”

Hypertensive disorders of pregnancy and chronic hypertension remain among the leading causes of maternal morbidity and mortality in the United States and worldwide.¹ The postpartum period remains a particularly high-risk time since up to 40% of maternal mortality can occur after delivery. To that end, the 2013 American College of Obstetricians and Gynecologists Hypertension in Pregnancy Task Force recommends postpartum follow-up 7 to 10 days after delivery in women with a hypertensive disorder of pregnancy.²

Why we need to find an alternative approach

Unfortunately, these guidelines are both cumbersome and insufficient. Up to one-third of patients do not attend their postpartum visit, particularly those who are young, uninsured, and nonwhite, a list uncomfortably similar to that for women most at risk for adverse outcomes after a high-risk pregnancy. In addition, the 7- to 10-day visit still represents only a single snapshot of the patient’s BP values rather than an ongoing assessment of symptoms or BP elevation over time. Moreover, studies also have shown that BP in both normotensive and hypertensive women often rises by the fifth day postpartum, suggesting that leaving this large window of time without surveillance may miss an opportunity to detect elevated BP in a more timely manner.³

It is time to break the habit of the in-office postpartum BP check and to evaluate the patient where she is and when she needs it. Research in the last 2 years shows that there are several solutions to our case patient’s question.

Solution 1: The provider-driven system

“Of course. Text us your numbers, and you will hear from the doctor if you need to do anything differently.”

One method that addresses both the communication and safety issues inherent in the 7- to 10-day routine in-office BP check is to have the patient send in her BP measurements for direct clinician review.

Researchers at the University of Pennsylvania developed a robust program using their Way to Health platform.⁴ Participating patients text their BP values twice daily, and they receive automated feedback for all values, with additional human feedback in real time from a clinician for severe-range values (>160 mm Hg systolic or >110 mm Hg diastolic). As an added safety measure, a physician reviews all inputted BPs daily and assesses the need for antihypertensive medication for BPs in the high mild range. Using this protocol, the researchers achieved a significant increase in adherence with the recommendation for reporting a BP value in the first 10 days after discharge (from 44% to 92%) as well as having fewer readmissions in the text-messaging arm (4% vs 0%).

Perhaps most impressive, though, is that the technology use eliminated pre-existing racial disparities in adherence. Black participants were as likely as nonblack participants to report a postpartum BP in the text-messaging system (93% vs 91%) despite being less than half as likely to keep a BP check visit (33% vs 70%).⁵

A similar solution is in place at the University of Pittsburgh, where a text message system on the Vivify platform is used to deliver patient BP measurements to a centralized monitoring team.⁶ This program is unique in that, rather than relying on a single physician, it is run through a nurse “call center” that allowed them to expand to 3 hospitals with the use of a single centralized monitoring team. To date, the program has enrolled more than 2,000 patients and achieved patient satisfaction rates greater than 94%.

A final program to consider was developed and piloted at the University of Wisconsin with an added technological advance: the use of a Bluetooth-enabled BP cuff that permits values to be automatically transmitted to a tablet that then uploads the information to a centralized database.⁷ This database was in turn monitored by trained nurses for safety and initiation or titration of antihypertensive medication as needed. Similar to the experience at the University of Pennsylvania, the researchers found improved adherence with monitoring and a notable reduction in readmissions (3.7% in controls vs 0.5% in the intervention arm). Of note, among those who did receive the ongoing monitoring, severe hypertension occurred in 56 (26.2%) of those patients and did so a mean of 6 days after discharge (that is, prior to when they typically would have seen a provider.)

The promise of such provider-driven systems is that they represent a true chronicle of a patient’s ongoing clinical course rather than a single snapshot of her BP in an artificial environment (and often after the highest risk time period!). In addition, direct monitoring by clinicians ensures an optimal safety profile.

Such systems, however, are also extremely resource intense in terms of both upfront information technology investment and ongoing provider surveillance. The systems above also relied on giving the patients a BP cuff, so it is unclear whether it was the technology support or this simple intervention that yielded the benefits. Nonetheless, the benefits were undeniable, and the financial costs saved by reducing even 1 hospital admission as well as the costs of outpatient surveillance may in the end justify these upfront expenditures.

Continue to: Solution 2: The algorithm-driven system...

Solution 2: The algorithm-driven system

“Sure. Plug your numbers into our system, and you’ll receive an automated response as to what to do next.”

One way to alleviate both the financial and opportunity cost of constant clinician surveillance would be to offload some tasks to algorithmic support. This approach—home BP monitoring accompanied by self-titration of antihypertensive medication—has been validated in outpatient primary care hypertension management in nonpregnant adults and more recently for postpartum patients as well.

In the SNAP-HT trial, investigators randomly assigned women to either usual care or algorithm-driven outpatient BP management.⁸ While both groups had serial visits (for safety monitoring), those in the experimental arm were advised only by the algorithm for any ongoing titration of medication. At 6 weeks, the investigators found that BPs were lower in the intervention group, and diastolic BPs remained lower at 6 months.

This methodology emphasizes the potential utility of true self-management of hypertension in the postpartum period. It relies, however, on having a highly developed system in place that can receive the data, respond with recommendations, and safely monitor for any aberrations in the feed. Still, this hybrid method may represent the sweet spot: a combination that ensures adequate surveillance while not overburdening the clinician with the simpler, initial steps in postpartum antihypertensive management.

Solution 3: The DIY system

“That’s a good point. I want to hear about your blood pressure readings in the meantime. Here’s what we can do.”

What about the 99% of practicing ObGyns who do not have an entire connected system for remote hypertension monitoring? A number of options can be put in place today with little cost and even less tech know-how (see “Do-it-yourself options for remote blood pressure monitoring,” below). Note that since many of these options would not be monitored in “real time” like the connected systems discussed above, the patient should be given strict parameters for contacting her clinician directly. These do-it-yourself, or DIY, methods are instead best for the purpose of chronic monitoring and medication titration but are still an improvement in communication over the single-serve BP check.

The bottom line

Pregnant women represent one of the most connected, Internet-savvy demographic groups of any patient population: More than three-quarters of pregnant women turn to the Internet for advice during their pregnancy.^9,10 In addition, unlike most social determinants of health, such as housing, food access, and health care coverage, access to connected electronic devices differs little across racial lines, suggesting the potential for targeting health care inequities by implementing more—not less—technology into prenatal and postpartum care.

For this generation of new mothers, the in-office postpartum BP check is insufficient, artificial, and simply a waste of everyone’s time. While there is no one-size-fits-all approach, there are many options, and it is up to us as health care providers to facilitate the right care, in the right place, at the right time for our patients. ●

Acknowledgements: The authors would like to thank Haritha Pavuluri, Margaret Oliver, and Samantha Boniface for their assistance in the preparation of this manuscript.

CASE Patient questions need for postpartum BP check

Ms. P presents at 28 weeks’ gestation with superimposed preeclampsia. She receives antenatal corticosteroids and titration of her nifedipine, but she is delivered at 29 weeks because of worsening fetal status. Her physician recommends a blood pressure (BP) visit in the office at 7 days postpartum.

She asks, “But can’t I just call you with the BP reading? And what do I do in the meantime?”

Hypertensive disorders of pregnancy and chronic hypertension remain among the leading causes of maternal morbidity and mortality in the United States and worldwide.¹ The postpartum period remains a particularly high-risk time since up to 40% of maternal mortality can occur after delivery. To that end, the 2013 American College of Obstetricians and Gynecologists Hypertension in Pregnancy Task Force recommends postpartum follow-up 7 to 10 days after delivery in women with a hypertensive disorder of pregnancy.²

Why we need to find an alternative approach

Unfortunately, these guidelines are both cumbersome and insufficient. Up to one-third of patients do not attend their postpartum visit, particularly those who are young, uninsured, and nonwhite, a list uncomfortably similar to that for women most at risk for adverse outcomes after a high-risk pregnancy. In addition, the 7- to 10-day visit still represents only a single snapshot of the patient’s BP values rather than an ongoing assessment of symptoms or BP elevation over time. Moreover, studies also have shown that BP in both normotensive and hypertensive women often rises by the fifth day postpartum, suggesting that leaving this large window of time without surveillance may miss an opportunity to detect elevated BP in a more timely manner.³

It is time to break the habit of the in-office postpartum BP check and to evaluate the patient where she is and when she needs it. Research in the last 2 years shows that there are several solutions to our case patient’s question.

Solution 1: The provider-driven system

“Of course. Text us your numbers, and you will hear from the doctor if you need to do anything differently.”

One method that addresses both the communication and safety issues inherent in the 7- to 10-day routine in-office BP check is to have the patient send in her BP measurements for direct clinician review.

Researchers at the University of Pennsylvania developed a robust program using their Way to Health platform.⁴ Participating patients text their BP values twice daily, and they receive automated feedback for all values, with additional human feedback in real time from a clinician for severe-range values (>160 mm Hg systolic or >110 mm Hg diastolic). As an added safety measure, a physician reviews all inputted BPs daily and assesses the need for antihypertensive medication for BPs in the high mild range. Using this protocol, the researchers achieved a significant increase in adherence with the recommendation for reporting a BP value in the first 10 days after discharge (from 44% to 92%) as well as having fewer readmissions in the text-messaging arm (4% vs 0%).

Perhaps most impressive, though, is that the technology use eliminated pre-existing racial disparities in adherence. Black participants were as likely as nonblack participants to report a postpartum BP in the text-messaging system (93% vs 91%) despite being less than half as likely to keep a BP check visit (33% vs 70%).⁵

A similar solution is in place at the University of Pittsburgh, where a text message system on the Vivify platform is used to deliver patient BP measurements to a centralized monitoring team.⁶ This program is unique in that, rather than relying on a single physician, it is run through a nurse “call center” that allowed them to expand to 3 hospitals with the use of a single centralized monitoring team. To date, the program has enrolled more than 2,000 patients and achieved patient satisfaction rates greater than 94%.

A final program to consider was developed and piloted at the University of Wisconsin with an added technological advance: the use of a Bluetooth-enabled BP cuff that permits values to be automatically transmitted to a tablet that then uploads the information to a centralized database.⁷ This database was in turn monitored by trained nurses for safety and initiation or titration of antihypertensive medication as needed. Similar to the experience at the University of Pennsylvania, the researchers found improved adherence with monitoring and a notable reduction in readmissions (3.7% in controls vs 0.5% in the intervention arm). Of note, among those who did receive the ongoing monitoring, severe hypertension occurred in 56 (26.2%) of those patients and did so a mean of 6 days after discharge (that is, prior to when they typically would have seen a provider.)

The promise of such provider-driven systems is that they represent a true chronicle of a patient’s ongoing clinical course rather than a single snapshot of her BP in an artificial environment (and often after the highest risk time period!). In addition, direct monitoring by clinicians ensures an optimal safety profile.

Such systems, however, are also extremely resource intense in terms of both upfront information technology investment and ongoing provider surveillance. The systems above also relied on giving the patients a BP cuff, so it is unclear whether it was the technology support or this simple intervention that yielded the benefits. Nonetheless, the benefits were undeniable, and the financial costs saved by reducing even 1 hospital admission as well as the costs of outpatient surveillance may in the end justify these upfront expenditures.

Continue to: Solution 2: The algorithm-driven system...

Solution 2: The algorithm-driven system

“Sure. Plug your numbers into our system, and you’ll receive an automated response as to what to do next.”

One way to alleviate both the financial and opportunity cost of constant clinician surveillance would be to offload some tasks to algorithmic support. This approach—home BP monitoring accompanied by self-titration of antihypertensive medication—has been validated in outpatient primary care hypertension management in nonpregnant adults and more recently for postpartum patients as well.

In the SNAP-HT trial, investigators randomly assigned women to either usual care or algorithm-driven outpatient BP management.⁸ While both groups had serial visits (for safety monitoring), those in the experimental arm were advised only by the algorithm for any ongoing titration of medication. At 6 weeks, the investigators found that BPs were lower in the intervention group, and diastolic BPs remained lower at 6 months.

This methodology emphasizes the potential utility of true self-management of hypertension in the postpartum period. It relies, however, on having a highly developed system in place that can receive the data, respond with recommendations, and safely monitor for any aberrations in the feed. Still, this hybrid method may represent the sweet spot: a combination that ensures adequate surveillance while not overburdening the clinician with the simpler, initial steps in postpartum antihypertensive management.

Solution 3: The DIY system

“That’s a good point. I want to hear about your blood pressure readings in the meantime. Here’s what we can do.”

What about the 99% of practicing ObGyns who do not have an entire connected system for remote hypertension monitoring? A number of options can be put in place today with little cost and even less tech know-how (see “Do-it-yourself options for remote blood pressure monitoring,” below). Note that since many of these options would not be monitored in “real time” like the connected systems discussed above, the patient should be given strict parameters for contacting her clinician directly. These do-it-yourself, or DIY, methods are instead best for the purpose of chronic monitoring and medication titration but are still an improvement in communication over the single-serve BP check.

The bottom line

Pregnant women represent one of the most connected, Internet-savvy demographic groups of any patient population: More than three-quarters of pregnant women turn to the Internet for advice during their pregnancy.^9,10 In addition, unlike most social determinants of health, such as housing, food access, and health care coverage, access to connected electronic devices differs little across racial lines, suggesting the potential for targeting health care inequities by implementing more—not less—technology into prenatal and postpartum care.

For this generation of new mothers, the in-office postpartum BP check is insufficient, artificial, and simply a waste of everyone’s time. While there is no one-size-fits-all approach, there are many options, and it is up to us as health care providers to facilitate the right care, in the right place, at the right time for our patients. ●

Acknowledgements: The authors would like to thank Haritha Pavuluri, Margaret Oliver, and Samantha Boniface for their assistance in the preparation of this manuscript.

CASE Patient questions need for postpartum BP check

Ms. P presents at 28 weeks’ gestation with superimposed preeclampsia. She receives antenatal corticosteroids and titration of her nifedipine, but she is delivered at 29 weeks because of worsening fetal status. Her physician recommends a blood pressure (BP) visit in the office at 7 days postpartum.

She asks, “But can’t I just call you with the BP reading? And what do I do in the meantime?”

Hypertensive disorders of pregnancy and chronic hypertension remain among the leading causes of maternal morbidity and mortality in the United States and worldwide.¹ The postpartum period remains a particularly high-risk time since up to 40% of maternal mortality can occur after delivery. To that end, the 2013 American College of Obstetricians and Gynecologists Hypertension in Pregnancy Task Force recommends postpartum follow-up 7 to 10 days after delivery in women with a hypertensive disorder of pregnancy.²

Why we need to find an alternative approach

Unfortunately, these guidelines are both cumbersome and insufficient. Up to one-third of patients do not attend their postpartum visit, particularly those who are young, uninsured, and nonwhite, a list uncomfortably similar to that for women most at risk for adverse outcomes after a high-risk pregnancy. In addition, the 7- to 10-day visit still represents only a single snapshot of the patient’s BP values rather than an ongoing assessment of symptoms or BP elevation over time. Moreover, studies also have shown that BP in both normotensive and hypertensive women often rises by the fifth day postpartum, suggesting that leaving this large window of time without surveillance may miss an opportunity to detect elevated BP in a more timely manner.³

It is time to break the habit of the in-office postpartum BP check and to evaluate the patient where she is and when she needs it. Research in the last 2 years shows that there are several solutions to our case patient’s question.

Solution 1: The provider-driven system

“Of course. Text us your numbers, and you will hear from the doctor if you need to do anything differently.”

One method that addresses both the communication and safety issues inherent in the 7- to 10-day routine in-office BP check is to have the patient send in her BP measurements for direct clinician review.

Researchers at the University of Pennsylvania developed a robust program using their Way to Health platform.⁴ Participating patients text their BP values twice daily, and they receive automated feedback for all values, with additional human feedback in real time from a clinician for severe-range values (>160 mm Hg systolic or >110 mm Hg diastolic). As an added safety measure, a physician reviews all inputted BPs daily and assesses the need for antihypertensive medication for BPs in the high mild range. Using this protocol, the researchers achieved a significant increase in adherence with the recommendation for reporting a BP value in the first 10 days after discharge (from 44% to 92%) as well as having fewer readmissions in the text-messaging arm (4% vs 0%).

Perhaps most impressive, though, is that the technology use eliminated pre-existing racial disparities in adherence. Black participants were as likely as nonblack participants to report a postpartum BP in the text-messaging system (93% vs 91%) despite being less than half as likely to keep a BP check visit (33% vs 70%).⁵

A similar solution is in place at the University of Pittsburgh, where a text message system on the Vivify platform is used to deliver patient BP measurements to a centralized monitoring team.⁶ This program is unique in that, rather than relying on a single physician, it is run through a nurse “call center” that allowed them to expand to 3 hospitals with the use of a single centralized monitoring team. To date, the program has enrolled more than 2,000 patients and achieved patient satisfaction rates greater than 94%.

A final program to consider was developed and piloted at the University of Wisconsin with an added technological advance: the use of a Bluetooth-enabled BP cuff that permits values to be automatically transmitted to a tablet that then uploads the information to a centralized database.⁷ This database was in turn monitored by trained nurses for safety and initiation or titration of antihypertensive medication as needed. Similar to the experience at the University of Pennsylvania, the researchers found improved adherence with monitoring and a notable reduction in readmissions (3.7% in controls vs 0.5% in the intervention arm). Of note, among those who did receive the ongoing monitoring, severe hypertension occurred in 56 (26.2%) of those patients and did so a mean of 6 days after discharge (that is, prior to when they typically would have seen a provider.)

The promise of such provider-driven systems is that they represent a true chronicle of a patient’s ongoing clinical course rather than a single snapshot of her BP in an artificial environment (and often after the highest risk time period!). In addition, direct monitoring by clinicians ensures an optimal safety profile.

Such systems, however, are also extremely resource intense in terms of both upfront information technology investment and ongoing provider surveillance. The systems above also relied on giving the patients a BP cuff, so it is unclear whether it was the technology support or this simple intervention that yielded the benefits. Nonetheless, the benefits were undeniable, and the financial costs saved by reducing even 1 hospital admission as well as the costs of outpatient surveillance may in the end justify these upfront expenditures.

Continue to: Solution 2: The algorithm-driven system...

Solution 2: The algorithm-driven system

“Sure. Plug your numbers into our system, and you’ll receive an automated response as to what to do next.”

One way to alleviate both the financial and opportunity cost of constant clinician surveillance would be to offload some tasks to algorithmic support. This approach—home BP monitoring accompanied by self-titration of antihypertensive medication—has been validated in outpatient primary care hypertension management in nonpregnant adults and more recently for postpartum patients as well.

In the SNAP-HT trial, investigators randomly assigned women to either usual care or algorithm-driven outpatient BP management.⁸ While both groups had serial visits (for safety monitoring), those in the experimental arm were advised only by the algorithm for any ongoing titration of medication. At 6 weeks, the investigators found that BPs were lower in the intervention group, and diastolic BPs remained lower at 6 months.

This methodology emphasizes the potential utility of true self-management of hypertension in the postpartum period. It relies, however, on having a highly developed system in place that can receive the data, respond with recommendations, and safely monitor for any aberrations in the feed. Still, this hybrid method may represent the sweet spot: a combination that ensures adequate surveillance while not overburdening the clinician with the simpler, initial steps in postpartum antihypertensive management.

Solution 3: The DIY system

“That’s a good point. I want to hear about your blood pressure readings in the meantime. Here’s what we can do.”

What about the 99% of practicing ObGyns who do not have an entire connected system for remote hypertension monitoring? A number of options can be put in place today with little cost and even less tech know-how (see “Do-it-yourself options for remote blood pressure monitoring,” below). Note that since many of these options would not be monitored in “real time” like the connected systems discussed above, the patient should be given strict parameters for contacting her clinician directly. These do-it-yourself, or DIY, methods are instead best for the purpose of chronic monitoring and medication titration but are still an improvement in communication over the single-serve BP check.

The bottom line

Pregnant women represent one of the most connected, Internet-savvy demographic groups of any patient population: More than three-quarters of pregnant women turn to the Internet for advice during their pregnancy.^9,10 In addition, unlike most social determinants of health, such as housing, food access, and health care coverage, access to connected electronic devices differs little across racial lines, suggesting the potential for targeting health care inequities by implementing more—not less—technology into prenatal and postpartum care.

For this generation of new mothers, the in-office postpartum BP check is insufficient, artificial, and simply a waste of everyone’s time. While there is no one-size-fits-all approach, there are many options, and it is up to us as health care providers to facilitate the right care, in the right place, at the right time for our patients. ●

Acknowledgements: The authors would like to thank Haritha Pavuluri, Margaret Oliver, and Samantha Boniface for their assistance in the preparation of this manuscript.

Abnormal uterine bleeding (AUB) continues to be a top reason that women present for gynecologic care. In general, our approach to the management of AUB is to diagnose causes before we prescribe therapy and to offer conservative therapies initially and progress to more invasive measures if indicated.

In this Update, we highlight several new studies that provide evidence for preferential use of certain medical and surgical therapies. In considering conservative therapy for the treatment of AUB, we take a closer look at the efficacy of cyclic progestogens. Another important issue, as more types of endometrial ablation (EA) are being developed and are coming into the market, is the need for additional guidance regarding decisions about EA versus progestin-releasing intrauterine devices (IUDs). Lastly, an unintended consequence of an increased cesarean delivery rate is the development of isthmocele, also known as cesarean scar defect or uterine niche. These defects, which can be bothersome and cause abnormal bleeding, are treated with various techniques. Within the last year, 2 systematic reviews that compare the efficacy of several different approaches and provide guidance have been published.

Is it time to retire cyclic progestogens for the treatment of heavy menstrual bleeding?

Bofill Rodriguez M, Lethaby A, Low C, et al. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;(8):CD001016.

In a recent Cochrane Database Systematic Review, Bofill Rodriguez and colleagues looked at the efficacy, safety, and tolerability of oral progestogen therapy for heavy menstrual bleeding.¹ They considered progestogen (medroxyprogesterone acetate or norethisterone) in short-cycle use (7 to 10 days in the luteal phase) and long-cycle use (21 days per cycle) in a review of 15 randomized clinical trials (RCTs) that included a total of 1,071 women. As this topic had not been updated in 12 years, this review was essential in demonstrating changes that occurred over the past decade.

The primary outcomes of the analysis were menstrual blood loss and treatment satisfaction. Secondary outcomes included the number of days of bleeding, quality of life, adherence and acceptability of treatment, adverse events, and costs.

Classic progestogens fall short compared with newer approaches

Analysis of the data revealed that short-cycle progestogen was inferior to treatment with tranexamic acid, danazol, and the 65-µg progesterone-releasing IUD (Pg-IUD). Of note, the 65-µg Pg-IUD has been off the market since 2001, and danazol is rarely used in current practice. Furthermore, based on 2 trials, cyclic progestogens demonstrated no clear benefit over nonsteroidal anti-inflammatory drugs. Additionally, long-cycle progestogen therapy was found to be inferior to the 52-mg levonorgestrel-releasing IUD (LNG-IUD), tranexamic acid, and ormeloxifene.

It should be noted that the quality of evidence is still lacking for progestogen therapy, and this study's main limitation is bias, as the women and the researchers were aware of the treatments that were given. This review is helpful, however, for emphasizing the advantage of tranexamic acid and LNG-IUD use in clinical care.

The takeaway. Although it may not necessarily be time to retire the use of cyclic oral progestogens, the 52-mg LNG-IUD or tranexamic acid may be more successful for treating AUB in women who are appropriate candidates.

Continue to: Endometrial ablation...

Endometrial ablation: New evidence informs when it could (and could not) be the best option

Bergeron C, Laberge PY, Boutin A, et al. Endometrial ablation or resection versus levonorgestrel intra-uterine system for the treatment of women with heavy menstrual bleeding and a normal uterine cavity: a systematic review with meta-analysis. Hum Reprod Update. 2020;26:302-311.

Vitale SG, Ferrero S, Ciebiera M, et al. Hysteroscopic endometrial resection vs hysterectomy for abnormal uterine bleeding: impact on quality of life and sexuality. Evidence from a systematic review of randomized controlled trials. Curr Opin Obstet Gynecol. 2020;32:159-165.

Two systematic reviews evaluated the efficacy of EA in women with abnormal uterine bleeding. One compared EA with the LNG-IUD and reported on safety and efficacy, while the other compared EA with hysterectomy and reported on quality of life.

Bergeron and colleagues reviewed 13 studies that included 884 women to compare the efficacy and safety of EA or resection with the LNG-IUD for the treatment of premenopausal women with AUB.³ They found no significant differences between EA and the LNG-IUD in terms of subsequent hysterectomy (risk ratio [RR] = 1.3; 95% confidence interval [CI], 0.60-2.11). It was not surprising that, when looking at age, EA was associated with a higher risk for hysterectomy in women younger than age 42 (RR = 5.26; 95% CI, 1.21-22.91). Conversely, subsequent hysterectomy was less likely with EA compared to LNG-IUD use in women older than 42 years. However, statistical significance was not reached in the older group (RR = 0.51; 95% CI, 0.21-1.24).

In the systematic review by Vitale and colleagues, 9 studies met inclusion criteria for a comparison of EA and hysterectomy, with the objective of ascertaining improvement in quality of life and several other measures.⁴

Although there was significant heterogeneity between assessment tools, both treatment groups experienced similar improvements in quality of life during the first year. However, hysterectomy was more advantageous in terms of improving uterine bleeding and satisfaction in the long term when compared with EA.⁴

Continue to: Laparoscopy is best approach for isthomocele management, with caveats...

He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.

Vitale SG, Ludwin A, Vilos GA, et al. From hysteroscopy to laparoendoscopic surgery: what is the best surgical approach for symptomatic isthmocele? A systematic review and meta-analysis. Arch Gynecol Obstet. 2020;301:33-52.

The isthmocele (cesarean scar defect, uterine niche), a known complication of cesarean delivery, represents a myometrial defect in the anterior uterine wall that often presents as abnormal uterine bleeding. It also can be a site for pregnancy-related complications, such as invasive placentation, placenta previa, and uterine rupture.

Two systematic reviews compared surgical strategies for treating isthmocele, including laparoscopy, hysteroscopy, combined laparoscopy and hysteroscopy, laparotomy, and vaginal repair.

Laparoscopy reduced isthmocele-associated AUB better than other techniques

A review by He and colleagues analyzed data from 10 pertinent studies (4 RCTs and 6 observational studies) that included 858 patients in total.⁵ Treatments compared were laparoscopy, hysteroscopy, combined laparoscopy with hysteroscopy, and vaginal repair for reduction of AUB and isthmocele and diverticulum depth.

The authors found no difference in intraoperative bleeding between the 4 surgical methods (laparotomy was not included in this review). Hysteroscopic surgery was associated with the shortest operative time, while laparoscopy was the longest surgery. In terms of reducing intermittent abnormal bleeding and scar depth, laparoscopic surgery performed better than the other 3 methods.

Approach considerations in isthmocele repair

Vitale and colleagues conducted a systematic review that included 33 publications (28 focused on a single surgical technique, 5 compared different techniques) to examine the effectiveness and risks of various surgical approaches for isthmocele in women with AUB, infertility, or for prevention of obstetric complications.⁶

Results of their analysis in general favored a laparoscopic approach for patients who desired future fertility, with an improvement rate of 92.7%. Hysteroscopic correction had an 85% improvement rate, and vaginal correction had an 82.5% improvement rate.

Although there were no high-level data to suggest a threshold for myometrial thickness in recommending a surgical approach, the authors provided a helpful algorithm for choosing a route based on a patient's fertility desires. For the asymptomatic patient, they suggest no treatment. In symptomatic patients, the laparoscopic approach is the gold standard but requires significant laparoscopic surgical skill, and a hysteroscopic approach may be considered as an alternative route if the residual myometrial defect is greater than 2.5 to 3.5 mm. For patients who are not considering future reproduction, hysteroscopy is the gold standard as long as the residual myometrial thickness is greater than 2.5 to 3.5 mm.

The takeaway. Of the several methods used for surgical isthmocele management, the laparoscopic approach reduced intermittent abnormal bleeding and scar depth better than other methods. It also was associated with the longest surgical duration. Hysteroscopic surgery was the quickest procedure to perform and is effective in removing the upper valve to promote the elimination of the hematocele and symptoms of abnormal bleeding; however, it does not change the anatomic aspects of the isthmocele in terms of myometrial thickness. Some authors suggested that deciding on the surgical route should be based on fertility desires and the residual thickness of the myometrium. ●

Abnormal uterine bleeding (AUB) continues to be a top reason that women present for gynecologic care. In general, our approach to the management of AUB is to diagnose causes before we prescribe therapy and to offer conservative therapies initially and progress to more invasive measures if indicated.

In this Update, we highlight several new studies that provide evidence for preferential use of certain medical and surgical therapies. In considering conservative therapy for the treatment of AUB, we take a closer look at the efficacy of cyclic progestogens. Another important issue, as more types of endometrial ablation (EA) are being developed and are coming into the market, is the need for additional guidance regarding decisions about EA versus progestin-releasing intrauterine devices (IUDs). Lastly, an unintended consequence of an increased cesarean delivery rate is the development of isthmocele, also known as cesarean scar defect or uterine niche. These defects, which can be bothersome and cause abnormal bleeding, are treated with various techniques. Within the last year, 2 systematic reviews that compare the efficacy of several different approaches and provide guidance have been published.

Is it time to retire cyclic progestogens for the treatment of heavy menstrual bleeding?

Bofill Rodriguez M, Lethaby A, Low C, et al. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;(8):CD001016.

In a recent Cochrane Database Systematic Review, Bofill Rodriguez and colleagues looked at the efficacy, safety, and tolerability of oral progestogen therapy for heavy menstrual bleeding.¹ They considered progestogen (medroxyprogesterone acetate or norethisterone) in short-cycle use (7 to 10 days in the luteal phase) and long-cycle use (21 days per cycle) in a review of 15 randomized clinical trials (RCTs) that included a total of 1,071 women. As this topic had not been updated in 12 years, this review was essential in demonstrating changes that occurred over the past decade.

The primary outcomes of the analysis were menstrual blood loss and treatment satisfaction. Secondary outcomes included the number of days of bleeding, quality of life, adherence and acceptability of treatment, adverse events, and costs.

Classic progestogens fall short compared with newer approaches

Analysis of the data revealed that short-cycle progestogen was inferior to treatment with tranexamic acid, danazol, and the 65-µg progesterone-releasing IUD (Pg-IUD). Of note, the 65-µg Pg-IUD has been off the market since 2001, and danazol is rarely used in current practice. Furthermore, based on 2 trials, cyclic progestogens demonstrated no clear benefit over nonsteroidal anti-inflammatory drugs. Additionally, long-cycle progestogen therapy was found to be inferior to the 52-mg levonorgestrel-releasing IUD (LNG-IUD), tranexamic acid, and ormeloxifene.

It should be noted that the quality of evidence is still lacking for progestogen therapy, and this study's main limitation is bias, as the women and the researchers were aware of the treatments that were given. This review is helpful, however, for emphasizing the advantage of tranexamic acid and LNG-IUD use in clinical care.

The takeaway. Although it may not necessarily be time to retire the use of cyclic oral progestogens, the 52-mg LNG-IUD or tranexamic acid may be more successful for treating AUB in women who are appropriate candidates.

Continue to: Endometrial ablation...

Endometrial ablation: New evidence informs when it could (and could not) be the best option

Bergeron C, Laberge PY, Boutin A, et al. Endometrial ablation or resection versus levonorgestrel intra-uterine system for the treatment of women with heavy menstrual bleeding and a normal uterine cavity: a systematic review with meta-analysis. Hum Reprod Update. 2020;26:302-311.

Vitale SG, Ferrero S, Ciebiera M, et al. Hysteroscopic endometrial resection vs hysterectomy for abnormal uterine bleeding: impact on quality of life and sexuality. Evidence from a systematic review of randomized controlled trials. Curr Opin Obstet Gynecol. 2020;32:159-165.

Two systematic reviews evaluated the efficacy of EA in women with abnormal uterine bleeding. One compared EA with the LNG-IUD and reported on safety and efficacy, while the other compared EA with hysterectomy and reported on quality of life.

Bergeron and colleagues reviewed 13 studies that included 884 women to compare the efficacy and safety of EA or resection with the LNG-IUD for the treatment of premenopausal women with AUB.³ They found no significant differences between EA and the LNG-IUD in terms of subsequent hysterectomy (risk ratio [RR] = 1.3; 95% confidence interval [CI], 0.60-2.11). It was not surprising that, when looking at age, EA was associated with a higher risk for hysterectomy in women younger than age 42 (RR = 5.26; 95% CI, 1.21-22.91). Conversely, subsequent hysterectomy was less likely with EA compared to LNG-IUD use in women older than 42 years. However, statistical significance was not reached in the older group (RR = 0.51; 95% CI, 0.21-1.24).

In the systematic review by Vitale and colleagues, 9 studies met inclusion criteria for a comparison of EA and hysterectomy, with the objective of ascertaining improvement in quality of life and several other measures.⁴

Although there was significant heterogeneity between assessment tools, both treatment groups experienced similar improvements in quality of life during the first year. However, hysterectomy was more advantageous in terms of improving uterine bleeding and satisfaction in the long term when compared with EA.⁴

Continue to: Laparoscopy is best approach for isthomocele management, with caveats...

He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.

Vitale SG, Ludwin A, Vilos GA, et al. From hysteroscopy to laparoendoscopic surgery: what is the best surgical approach for symptomatic isthmocele? A systematic review and meta-analysis. Arch Gynecol Obstet. 2020;301:33-52.

The isthmocele (cesarean scar defect, uterine niche), a known complication of cesarean delivery, represents a myometrial defect in the anterior uterine wall that often presents as abnormal uterine bleeding. It also can be a site for pregnancy-related complications, such as invasive placentation, placenta previa, and uterine rupture.

Two systematic reviews compared surgical strategies for treating isthmocele, including laparoscopy, hysteroscopy, combined laparoscopy and hysteroscopy, laparotomy, and vaginal repair.

Laparoscopy reduced isthmocele-associated AUB better than other techniques

A review by He and colleagues analyzed data from 10 pertinent studies (4 RCTs and 6 observational studies) that included 858 patients in total.⁵ Treatments compared were laparoscopy, hysteroscopy, combined laparoscopy with hysteroscopy, and vaginal repair for reduction of AUB and isthmocele and diverticulum depth.

The authors found no difference in intraoperative bleeding between the 4 surgical methods (laparotomy was not included in this review). Hysteroscopic surgery was associated with the shortest operative time, while laparoscopy was the longest surgery. In terms of reducing intermittent abnormal bleeding and scar depth, laparoscopic surgery performed better than the other 3 methods.

Approach considerations in isthmocele repair

Vitale and colleagues conducted a systematic review that included 33 publications (28 focused on a single surgical technique, 5 compared different techniques) to examine the effectiveness and risks of various surgical approaches for isthmocele in women with AUB, infertility, or for prevention of obstetric complications.⁶

Results of their analysis in general favored a laparoscopic approach for patients who desired future fertility, with an improvement rate of 92.7%. Hysteroscopic correction had an 85% improvement rate, and vaginal correction had an 82.5% improvement rate.

Although there were no high-level data to suggest a threshold for myometrial thickness in recommending a surgical approach, the authors provided a helpful algorithm for choosing a route based on a patient's fertility desires. For the asymptomatic patient, they suggest no treatment. In symptomatic patients, the laparoscopic approach is the gold standard but requires significant laparoscopic surgical skill, and a hysteroscopic approach may be considered as an alternative route if the residual myometrial defect is greater than 2.5 to 3.5 mm. For patients who are not considering future reproduction, hysteroscopy is the gold standard as long as the residual myometrial thickness is greater than 2.5 to 3.5 mm.

The takeaway. Of the several methods used for surgical isthmocele management, the laparoscopic approach reduced intermittent abnormal bleeding and scar depth better than other methods. It also was associated with the longest surgical duration. Hysteroscopic surgery was the quickest procedure to perform and is effective in removing the upper valve to promote the elimination of the hematocele and symptoms of abnormal bleeding; however, it does not change the anatomic aspects of the isthmocele in terms of myometrial thickness. Some authors suggested that deciding on the surgical route should be based on fertility desires and the residual thickness of the myometrium. ●

Abnormal uterine bleeding (AUB) continues to be a top reason that women present for gynecologic care. In general, our approach to the management of AUB is to diagnose causes before we prescribe therapy and to offer conservative therapies initially and progress to more invasive measures if indicated.

In this Update, we highlight several new studies that provide evidence for preferential use of certain medical and surgical therapies. In considering conservative therapy for the treatment of AUB, we take a closer look at the efficacy of cyclic progestogens. Another important issue, as more types of endometrial ablation (EA) are being developed and are coming into the market, is the need for additional guidance regarding decisions about EA versus progestin-releasing intrauterine devices (IUDs). Lastly, an unintended consequence of an increased cesarean delivery rate is the development of isthmocele, also known as cesarean scar defect or uterine niche. These defects, which can be bothersome and cause abnormal bleeding, are treated with various techniques. Within the last year, 2 systematic reviews that compare the efficacy of several different approaches and provide guidance have been published.

Is it time to retire cyclic progestogens for the treatment of heavy menstrual bleeding?

Bofill Rodriguez M, Lethaby A, Low C, et al. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;(8):CD001016.

In a recent Cochrane Database Systematic Review, Bofill Rodriguez and colleagues looked at the efficacy, safety, and tolerability of oral progestogen therapy for heavy menstrual bleeding.¹ They considered progestogen (medroxyprogesterone acetate or norethisterone) in short-cycle use (7 to 10 days in the luteal phase) and long-cycle use (21 days per cycle) in a review of 15 randomized clinical trials (RCTs) that included a total of 1,071 women. As this topic had not been updated in 12 years, this review was essential in demonstrating changes that occurred over the past decade.

The primary outcomes of the analysis were menstrual blood loss and treatment satisfaction. Secondary outcomes included the number of days of bleeding, quality of life, adherence and acceptability of treatment, adverse events, and costs.

Classic progestogens fall short compared with newer approaches

Analysis of the data revealed that short-cycle progestogen was inferior to treatment with tranexamic acid, danazol, and the 65-µg progesterone-releasing IUD (Pg-IUD). Of note, the 65-µg Pg-IUD has been off the market since 2001, and danazol is rarely used in current practice. Furthermore, based on 2 trials, cyclic progestogens demonstrated no clear benefit over nonsteroidal anti-inflammatory drugs. Additionally, long-cycle progestogen therapy was found to be inferior to the 52-mg levonorgestrel-releasing IUD (LNG-IUD), tranexamic acid, and ormeloxifene.

It should be noted that the quality of evidence is still lacking for progestogen therapy, and this study's main limitation is bias, as the women and the researchers were aware of the treatments that were given. This review is helpful, however, for emphasizing the advantage of tranexamic acid and LNG-IUD use in clinical care.

The takeaway. Although it may not necessarily be time to retire the use of cyclic oral progestogens, the 52-mg LNG-IUD or tranexamic acid may be more successful for treating AUB in women who are appropriate candidates.

Continue to: Endometrial ablation...

Endometrial ablation: New evidence informs when it could (and could not) be the best option

Bergeron C, Laberge PY, Boutin A, et al. Endometrial ablation or resection versus levonorgestrel intra-uterine system for the treatment of women with heavy menstrual bleeding and a normal uterine cavity: a systematic review with meta-analysis. Hum Reprod Update. 2020;26:302-311.

Vitale SG, Ferrero S, Ciebiera M, et al. Hysteroscopic endometrial resection vs hysterectomy for abnormal uterine bleeding: impact on quality of life and sexuality. Evidence from a systematic review of randomized controlled trials. Curr Opin Obstet Gynecol. 2020;32:159-165.

Two systematic reviews evaluated the efficacy of EA in women with abnormal uterine bleeding. One compared EA with the LNG-IUD and reported on safety and efficacy, while the other compared EA with hysterectomy and reported on quality of life.

Bergeron and colleagues reviewed 13 studies that included 884 women to compare the efficacy and safety of EA or resection with the LNG-IUD for the treatment of premenopausal women with AUB.³ They found no significant differences between EA and the LNG-IUD in terms of subsequent hysterectomy (risk ratio [RR] = 1.3; 95% confidence interval [CI], 0.60-2.11). It was not surprising that, when looking at age, EA was associated with a higher risk for hysterectomy in women younger than age 42 (RR = 5.26; 95% CI, 1.21-22.91). Conversely, subsequent hysterectomy was less likely with EA compared to LNG-IUD use in women older than 42 years. However, statistical significance was not reached in the older group (RR = 0.51; 95% CI, 0.21-1.24).

In the systematic review by Vitale and colleagues, 9 studies met inclusion criteria for a comparison of EA and hysterectomy, with the objective of ascertaining improvement in quality of life and several other measures.⁴

Although there was significant heterogeneity between assessment tools, both treatment groups experienced similar improvements in quality of life during the first year. However, hysterectomy was more advantageous in terms of improving uterine bleeding and satisfaction in the long term when compared with EA.⁴

Continue to: Laparoscopy is best approach for isthomocele management, with caveats...

He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.

Vitale SG, Ludwin A, Vilos GA, et al. From hysteroscopy to laparoendoscopic surgery: what is the best surgical approach for symptomatic isthmocele? A systematic review and meta-analysis. Arch Gynecol Obstet. 2020;301:33-52.

The isthmocele (cesarean scar defect, uterine niche), a known complication of cesarean delivery, represents a myometrial defect in the anterior uterine wall that often presents as abnormal uterine bleeding. It also can be a site for pregnancy-related complications, such as invasive placentation, placenta previa, and uterine rupture.

Two systematic reviews compared surgical strategies for treating isthmocele, including laparoscopy, hysteroscopy, combined laparoscopy and hysteroscopy, laparotomy, and vaginal repair.

Laparoscopy reduced isthmocele-associated AUB better than other techniques

A review by He and colleagues analyzed data from 10 pertinent studies (4 RCTs and 6 observational studies) that included 858 patients in total.⁵ Treatments compared were laparoscopy, hysteroscopy, combined laparoscopy with hysteroscopy, and vaginal repair for reduction of AUB and isthmocele and diverticulum depth.

The authors found no difference in intraoperative bleeding between the 4 surgical methods (laparotomy was not included in this review). Hysteroscopic surgery was associated with the shortest operative time, while laparoscopy was the longest surgery. In terms of reducing intermittent abnormal bleeding and scar depth, laparoscopic surgery performed better than the other 3 methods.

Approach considerations in isthmocele repair

Vitale and colleagues conducted a systematic review that included 33 publications (28 focused on a single surgical technique, 5 compared different techniques) to examine the effectiveness and risks of various surgical approaches for isthmocele in women with AUB, infertility, or for prevention of obstetric complications.⁶

Results of their analysis in general favored a laparoscopic approach for patients who desired future fertility, with an improvement rate of 92.7%. Hysteroscopic correction had an 85% improvement rate, and vaginal correction had an 82.5% improvement rate.

Although there were no high-level data to suggest a threshold for myometrial thickness in recommending a surgical approach, the authors provided a helpful algorithm for choosing a route based on a patient's fertility desires. For the asymptomatic patient, they suggest no treatment. In symptomatic patients, the laparoscopic approach is the gold standard but requires significant laparoscopic surgical skill, and a hysteroscopic approach may be considered as an alternative route if the residual myometrial defect is greater than 2.5 to 3.5 mm. For patients who are not considering future reproduction, hysteroscopy is the gold standard as long as the residual myometrial thickness is greater than 2.5 to 3.5 mm.

The takeaway. Of the several methods used for surgical isthmocele management, the laparoscopic approach reduced intermittent abnormal bleeding and scar depth better than other methods. It also was associated with the longest surgical duration. Hysteroscopic surgery was the quickest procedure to perform and is effective in removing the upper valve to promote the elimination of the hematocele and symptoms of abnormal bleeding; however, it does not change the anatomic aspects of the isthmocele in terms of myometrial thickness. Some authors suggested that deciding on the surgical route should be based on fertility desires and the residual thickness of the myometrium. ●