Polycystic ovarian syndrome (PCOS) was associated with a nearly doubled risk of developing psoriasis in a propensity score–matched analysis conducted in Taiwan.

PCOS is characterized by androgen elevation that can lead to insulin resistance and metabolic syndrome, which have also been associated with an increased risk of psoriasis. Previous retrospective analyses have suggested an increased risk of psoriasis associated with PCOS, and psoriasis patients with PCOS have been reported to have more severe skin lesions, compared with those who do not have PCOS.

“The incidence of psoriasis is indeed higher in the PCOS group than in the control group, and the comorbidities related to metabolic syndrome did not modify the adjusted hazard ratio,” said Ming-Li Chen, during her presentation of the study results at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Dr. Chen is at Chung Shan Medical University in Taiwan.

The researchers analyzed 1 million randomly selected records from Taiwan’s Longitudinal Health Insurance database, a subset of the country’s National Health Insurance Program. Between 2000 and 2012, they identified a case group with at least three outpatient diagnoses or one inpatient diagnosis of PCOS; they then compared each with four patients who did not have PCOS who were matched by age and index year. The mean age in both groups was about 27 years.

The mean follow-up times were 6.99 years for 4,707 cases and 6.94 years for 18,828 controls. Comorbidities were slightly higher in the PCOS group, including asthma (6.7% vs. 4.9%; P less than .001), chronic obstructive pulmonary disease (14% vs. 11%; P less than .001), chronic liver disease (8.0% vs. 5.0%; P less than .001), diabetes mellitus (3.0% vs. 1.4%; P less than .001), hypertension (2.4% vs. 1.5%; P less than .001), hyperlipidemia (5.4% vs. 2.5%; P less than .001), depression (5.4% vs. 3.9%; P less than .001), and sleep apnea (0.23% vs. 0.10%; P = .040).

There was a higher cumulative incidence of psoriasis in the PCOS group (adjusted hazard ratio, 2.07; 95% confidence interval, 1.25-3.44). Other factors associated with increased risk of psoriasis were advanced age (greater than 50 years old; aHR, 14.13; 95% CI, 1.8-110.7) and having a cancer diagnosis (aHR, 11.72; 95% CI, 2.87-47.9).

When PCOS patients were stratified by age, the researchers noted a higher risk of psoriasis among those 20 years or younger (aHR, 4.02; 95% CI, 1.16-13.9) than among those aged 20-50 years (aHR, 1.88; 95% CI, 1.07-3.29). Among those older than 50 years, there was no significantly increased risk, although the number of psoriasis diagnoses and population sizes were small in the latter category. Among patients with PCOS, a cancer diagnosis was not associated with a statistically significant increased risk of psoriasis.

The mechanisms underlying the association between PCOS and psoriasis should be studied further, she noted.

Following Dr. Chen’s prerecorded presentation, there was a live discussion session led by Alice Gottlieb, MD, PhD, medical director of Mount Sinai Beth Israel Dermatology, New York, and Ennio Lubrano, MD, associate professor of rheumatology at the University of Molise (Italy). Dr. Gottlieb noted that the study did not appear to account for weight in the association between PCOS and psoriasis, since heavier people are known to be at greater risk of developing psoriasis. Dr. Chen acknowledged that the study had no records of BMI or weight.

Dr. Gottlieb also wondered if treatment of PCOS led to any improvements in psoriasis in patients with the two diagnoses. “If we treat PCOS, does the psoriasis get better?” Again, the study did not address the question. “We didn’t follow up on therapies,” Dr. Chen said.

Dr. Chen reported no relevant financial disclosures. Dr. Gottlieb is a consultant, advisory board member and/or speaker for AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Incyte, Janssen, Leo, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB Pharma and Xbiotech. She has received research or educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis and Xbiotech.

Polycystic ovarian syndrome (PCOS) was associated with a nearly doubled risk of developing psoriasis in a propensity score–matched analysis conducted in Taiwan.

PCOS is characterized by androgen elevation that can lead to insulin resistance and metabolic syndrome, which have also been associated with an increased risk of psoriasis. Previous retrospective analyses have suggested an increased risk of psoriasis associated with PCOS, and psoriasis patients with PCOS have been reported to have more severe skin lesions, compared with those who do not have PCOS.

“The incidence of psoriasis is indeed higher in the PCOS group than in the control group, and the comorbidities related to metabolic syndrome did not modify the adjusted hazard ratio,” said Ming-Li Chen, during her presentation of the study results at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Dr. Chen is at Chung Shan Medical University in Taiwan.

The researchers analyzed 1 million randomly selected records from Taiwan’s Longitudinal Health Insurance database, a subset of the country’s National Health Insurance Program. Between 2000 and 2012, they identified a case group with at least three outpatient diagnoses or one inpatient diagnosis of PCOS; they then compared each with four patients who did not have PCOS who were matched by age and index year. The mean age in both groups was about 27 years.

The mean follow-up times were 6.99 years for 4,707 cases and 6.94 years for 18,828 controls. Comorbidities were slightly higher in the PCOS group, including asthma (6.7% vs. 4.9%; P less than .001), chronic obstructive pulmonary disease (14% vs. 11%; P less than .001), chronic liver disease (8.0% vs. 5.0%; P less than .001), diabetes mellitus (3.0% vs. 1.4%; P less than .001), hypertension (2.4% vs. 1.5%; P less than .001), hyperlipidemia (5.4% vs. 2.5%; P less than .001), depression (5.4% vs. 3.9%; P less than .001), and sleep apnea (0.23% vs. 0.10%; P = .040).

There was a higher cumulative incidence of psoriasis in the PCOS group (adjusted hazard ratio, 2.07; 95% confidence interval, 1.25-3.44). Other factors associated with increased risk of psoriasis were advanced age (greater than 50 years old; aHR, 14.13; 95% CI, 1.8-110.7) and having a cancer diagnosis (aHR, 11.72; 95% CI, 2.87-47.9).

When PCOS patients were stratified by age, the researchers noted a higher risk of psoriasis among those 20 years or younger (aHR, 4.02; 95% CI, 1.16-13.9) than among those aged 20-50 years (aHR, 1.88; 95% CI, 1.07-3.29). Among those older than 50 years, there was no significantly increased risk, although the number of psoriasis diagnoses and population sizes were small in the latter category. Among patients with PCOS, a cancer diagnosis was not associated with a statistically significant increased risk of psoriasis.

The mechanisms underlying the association between PCOS and psoriasis should be studied further, she noted.

Following Dr. Chen’s prerecorded presentation, there was a live discussion session led by Alice Gottlieb, MD, PhD, medical director of Mount Sinai Beth Israel Dermatology, New York, and Ennio Lubrano, MD, associate professor of rheumatology at the University of Molise (Italy). Dr. Gottlieb noted that the study did not appear to account for weight in the association between PCOS and psoriasis, since heavier people are known to be at greater risk of developing psoriasis. Dr. Chen acknowledged that the study had no records of BMI or weight.

Dr. Gottlieb also wondered if treatment of PCOS led to any improvements in psoriasis in patients with the two diagnoses. “If we treat PCOS, does the psoriasis get better?” Again, the study did not address the question. “We didn’t follow up on therapies,” Dr. Chen said.

Dr. Chen reported no relevant financial disclosures. Dr. Gottlieb is a consultant, advisory board member and/or speaker for AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Incyte, Janssen, Leo, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB Pharma and Xbiotech. She has received research or educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis and Xbiotech.

Polycystic ovarian syndrome (PCOS) was associated with a nearly doubled risk of developing psoriasis in a propensity score–matched analysis conducted in Taiwan.

PCOS is characterized by androgen elevation that can lead to insulin resistance and metabolic syndrome, which have also been associated with an increased risk of psoriasis. Previous retrospective analyses have suggested an increased risk of psoriasis associated with PCOS, and psoriasis patients with PCOS have been reported to have more severe skin lesions, compared with those who do not have PCOS.

“The incidence of psoriasis is indeed higher in the PCOS group than in the control group, and the comorbidities related to metabolic syndrome did not modify the adjusted hazard ratio,” said Ming-Li Chen, during her presentation of the study results at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Dr. Chen is at Chung Shan Medical University in Taiwan.

The researchers analyzed 1 million randomly selected records from Taiwan’s Longitudinal Health Insurance database, a subset of the country’s National Health Insurance Program. Between 2000 and 2012, they identified a case group with at least three outpatient diagnoses or one inpatient diagnosis of PCOS; they then compared each with four patients who did not have PCOS who were matched by age and index year. The mean age in both groups was about 27 years.

The mean follow-up times were 6.99 years for 4,707 cases and 6.94 years for 18,828 controls. Comorbidities were slightly higher in the PCOS group, including asthma (6.7% vs. 4.9%; P less than .001), chronic obstructive pulmonary disease (14% vs. 11%; P less than .001), chronic liver disease (8.0% vs. 5.0%; P less than .001), diabetes mellitus (3.0% vs. 1.4%; P less than .001), hypertension (2.4% vs. 1.5%; P less than .001), hyperlipidemia (5.4% vs. 2.5%; P less than .001), depression (5.4% vs. 3.9%; P less than .001), and sleep apnea (0.23% vs. 0.10%; P = .040).

There was a higher cumulative incidence of psoriasis in the PCOS group (adjusted hazard ratio, 2.07; 95% confidence interval, 1.25-3.44). Other factors associated with increased risk of psoriasis were advanced age (greater than 50 years old; aHR, 14.13; 95% CI, 1.8-110.7) and having a cancer diagnosis (aHR, 11.72; 95% CI, 2.87-47.9).

When PCOS patients were stratified by age, the researchers noted a higher risk of psoriasis among those 20 years or younger (aHR, 4.02; 95% CI, 1.16-13.9) than among those aged 20-50 years (aHR, 1.88; 95% CI, 1.07-3.29). Among those older than 50 years, there was no significantly increased risk, although the number of psoriasis diagnoses and population sizes were small in the latter category. Among patients with PCOS, a cancer diagnosis was not associated with a statistically significant increased risk of psoriasis.

The mechanisms underlying the association between PCOS and psoriasis should be studied further, she noted.

Following Dr. Chen’s prerecorded presentation, there was a live discussion session led by Alice Gottlieb, MD, PhD, medical director of Mount Sinai Beth Israel Dermatology, New York, and Ennio Lubrano, MD, associate professor of rheumatology at the University of Molise (Italy). Dr. Gottlieb noted that the study did not appear to account for weight in the association between PCOS and psoriasis, since heavier people are known to be at greater risk of developing psoriasis. Dr. Chen acknowledged that the study had no records of BMI or weight.

Dr. Gottlieb also wondered if treatment of PCOS led to any improvements in psoriasis in patients with the two diagnoses. “If we treat PCOS, does the psoriasis get better?” Again, the study did not address the question. “We didn’t follow up on therapies,” Dr. Chen said.

Dr. Chen reported no relevant financial disclosures. Dr. Gottlieb is a consultant, advisory board member and/or speaker for AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Incyte, Janssen, Leo, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB Pharma and Xbiotech. She has received research or educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis and Xbiotech.

Safe and effective new prescription topical therapies for primary axillary hyperhidrosis took a giant step closer to reaching clinical practice following positive reports from two phase 3, randomized, controlled trials of novel agents presented at the virtual annual meeting of the American Academy of Dermatology.

simarik/iStock/Getty Images

Both investigational topical anticholinergic agents – 5% sofpironium bromide (SPB) gel and 1% glycopyrronium bromide (GPB) cream – met all of the efficacy and safety endpoints required by the Food and Drug Administration.

Primary axillary hyperhidrosis, or symmetrical bilateral excessive armpit sweating, has a prevalence worldwide of 1%-16%, with 5%-6% the most frequently cited numbers. The condition has a strong adverse impact on quality of life. Primary axillary hyperhidrosis is not caused by a disorder of the sweat glands; rather, it’s actually a dysregulation of the autonomic nervous system leading to disproportionate sweating, explained Christoph Abels, MD, PhD, medical director at Dr. August Wolff in Bielefeld, Germany.

“What’s surprising is that more than 50% of patients do not receive appropriate treatment, very likely due to lack of awareness or embarrassment,” he added.

Also, many patients are put off by the systemic side effects of the oral anticholinergic agents, which are the current off-label treatment mainstay for patients with moderate or severe disease, according to Tomoko Fujimoto, MD, PhD, director of Ikebukuro Nishiguchi Fukurou Dermatology, near Tokyo.
 

Sofpironium bromide gel

Dr. Fujimoto presented the results of a phase 3, double-blind, multicenter, 6-week, vehicle-controlled clinical trial conducted in 281 Japanese patients with moderate to severe primary axillary hyperhidrosis as defined by a baseline score of 3 or 4 on the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Participants were randomized to self-application of 5% SPB gel or its vehicle once daily before bedtime.

Sofpironium bromide blocks the cholinergic response mediated by the M3 muscarinic receptor subtype expressed on eccrine sweat glands, thereby inhibiting sweating. The drug then undergoes breakdown into an inactive metabolite after reaching the blood.

An important aspect of both SPB gel and GPB cream is that these agents are rolled onto the axillae using a dedicated applicator. Patients never touch the medications with their hands, thus avoiding accidental exposure to the mucous membranes. This largely prevents problems with mydriasis and blurred vision as anticholinergic side effects, which has been an issue with glycopyrronium tosylate topical cloth wipes (Qbrexza), the first FDA-approved treatment for primary axillary hyperhidrosis.

The primary endpoint in the Japanese study was at least a 1-point improvement on the HDSS plus at least a 50% reduction in gravimetric sweat production between baseline and week 6. This composite outcome was achieved in 53.9% of patients in the active treatment arm, compared with 36.4% of controls.

The secondary endpoint consisting of a week-6 HDSS score of 1 or 2 – that is, underarm sweating that’s either never noticeable or is tolerable – occurred in 60.3% of the sofpironium bromide group and 47.9% of controls, a between-group difference that achieved statistical significance by week 2, when the rates were 46.8% and 28.2%.

The reduction in total gravimetric weight of axillary sweat from a mean baseline of 227 mg collected over 5 minutes was also significantly greater in the SPB group: a decrease of 157.6 mg, compared with 127.6 mg in controls; a between-group difference that also was significant by week 2. The mean Dermatology Life Quality Index score dropped by 6.8 points in the active-treatment arm from a baseline of 11.3, a significant improvement over the mean 4.5-point drop in controls.

A new 5-point measure of subjective symptoms of primary axillary hyperhidrosis – the Hyperhidrosis Disease Severity Measure–Axilla (HDSM-Ax) – improved by 1.41 points in the SPB group, significantly better than the 0.93 points in vehicle-treated controls. About 48% of patients on SBP experienced at least a 1.5-point reduction on the HDSM-Ax, compared with 26% of controls.

Regarding safety, there was a 2% incidence of application-site itch or scale in the SBP group. Anticholinergic side effects consisted of a single case of mydriasis, another of constipation, and two complaints of thirst, all mild, none resulting in treatment discontinuation. There were no reports of headache or blurred vision.

“These results indicate that the safety risks of sofpironium bromide can be considered small and controllable,” Dr. Fujimoto said. “Moreover, sofpironium bromide is a topical agent that patients can use by themselves, so it is highly convenient, unlike, say, botulinum toxin type A injections.”

Glycopyrronium bromide cream

Following on the heels of a recently published dose-ranging study (Br J Dermatol. 2020 Jan;182[1]:229-231), Dr. Abels presented the 4-week outcomes of a phase 3a, double-blind, randomized, five-country trial of once-daily 1% GPB cream or placebo in 171 patients with moderate or severe primary axillary hyperhidrosis. A phase 3b, open-label, 72-week, long-term safety trial is ongoing in 516 patients.

The primary endpoint of the 4-week trial was the reduction in gravimetric sweat production from day 1 to day 29. A reduction of 50% or more was documented in 57.5% of the patients on GBP and 34.5% of controls. A 75% or greater reduction occurred in 32.2% of the active-treatment group and 16.7% of those on placebo. And a decrease of at least 90% was seen in 23% of patients on topical GBP, compared with 9.5% of controls. All these between-group differences were significant.

The FDA now requires a quality of life measurement as a coprimary endpoint in phase 3 hyperhidrosis studies, and the phase 3 GBP trial also served as the successful validation study for a new patient-reported quality of life instrument designed specifically for this purpose. The new tool, known as the Hyperhydrosis Quality of Life questionnaire (HidroQol), proved much more sensitive than the HDSS or DLQI for evaluating clinical improvement in response to treatment (Br J Dermatol. 2020 Jun 8. doi: 10.1111/bjd.19300).

Initial results from the long-term phase 3b safety study should be available this fall on the first 100 patients followed on topical GBP for 1 year and for 300 followed for 6 months, Dr. Abels said.

Dr. Fujimoto reported serving as a paid consultant to and speaker for Kaken Pharmaceutical, which is developing SBP gel with Brickell Biotech. Dr. Abels is an employee of the company that is developing GPB cream.

[email protected]

Safe and effective new prescription topical therapies for primary axillary hyperhidrosis took a giant step closer to reaching clinical practice following positive reports from two phase 3, randomized, controlled trials of novel agents presented at the virtual annual meeting of the American Academy of Dermatology.

simarik/iStock/Getty Images

Both investigational topical anticholinergic agents – 5% sofpironium bromide (SPB) gel and 1% glycopyrronium bromide (GPB) cream – met all of the efficacy and safety endpoints required by the Food and Drug Administration.

Primary axillary hyperhidrosis, or symmetrical bilateral excessive armpit sweating, has a prevalence worldwide of 1%-16%, with 5%-6% the most frequently cited numbers. The condition has a strong adverse impact on quality of life. Primary axillary hyperhidrosis is not caused by a disorder of the sweat glands; rather, it’s actually a dysregulation of the autonomic nervous system leading to disproportionate sweating, explained Christoph Abels, MD, PhD, medical director at Dr. August Wolff in Bielefeld, Germany.

“What’s surprising is that more than 50% of patients do not receive appropriate treatment, very likely due to lack of awareness or embarrassment,” he added.

Also, many patients are put off by the systemic side effects of the oral anticholinergic agents, which are the current off-label treatment mainstay for patients with moderate or severe disease, according to Tomoko Fujimoto, MD, PhD, director of Ikebukuro Nishiguchi Fukurou Dermatology, near Tokyo.
 

Sofpironium bromide gel

Dr. Fujimoto presented the results of a phase 3, double-blind, multicenter, 6-week, vehicle-controlled clinical trial conducted in 281 Japanese patients with moderate to severe primary axillary hyperhidrosis as defined by a baseline score of 3 or 4 on the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Participants were randomized to self-application of 5% SPB gel or its vehicle once daily before bedtime.

Sofpironium bromide blocks the cholinergic response mediated by the M3 muscarinic receptor subtype expressed on eccrine sweat glands, thereby inhibiting sweating. The drug then undergoes breakdown into an inactive metabolite after reaching the blood.

An important aspect of both SPB gel and GPB cream is that these agents are rolled onto the axillae using a dedicated applicator. Patients never touch the medications with their hands, thus avoiding accidental exposure to the mucous membranes. This largely prevents problems with mydriasis and blurred vision as anticholinergic side effects, which has been an issue with glycopyrronium tosylate topical cloth wipes (Qbrexza), the first FDA-approved treatment for primary axillary hyperhidrosis.

The primary endpoint in the Japanese study was at least a 1-point improvement on the HDSS plus at least a 50% reduction in gravimetric sweat production between baseline and week 6. This composite outcome was achieved in 53.9% of patients in the active treatment arm, compared with 36.4% of controls.

The secondary endpoint consisting of a week-6 HDSS score of 1 or 2 – that is, underarm sweating that’s either never noticeable or is tolerable – occurred in 60.3% of the sofpironium bromide group and 47.9% of controls, a between-group difference that achieved statistical significance by week 2, when the rates were 46.8% and 28.2%.

The reduction in total gravimetric weight of axillary sweat from a mean baseline of 227 mg collected over 5 minutes was also significantly greater in the SPB group: a decrease of 157.6 mg, compared with 127.6 mg in controls; a between-group difference that also was significant by week 2. The mean Dermatology Life Quality Index score dropped by 6.8 points in the active-treatment arm from a baseline of 11.3, a significant improvement over the mean 4.5-point drop in controls.

A new 5-point measure of subjective symptoms of primary axillary hyperhidrosis – the Hyperhidrosis Disease Severity Measure–Axilla (HDSM-Ax) – improved by 1.41 points in the SPB group, significantly better than the 0.93 points in vehicle-treated controls. About 48% of patients on SBP experienced at least a 1.5-point reduction on the HDSM-Ax, compared with 26% of controls.

Regarding safety, there was a 2% incidence of application-site itch or scale in the SBP group. Anticholinergic side effects consisted of a single case of mydriasis, another of constipation, and two complaints of thirst, all mild, none resulting in treatment discontinuation. There were no reports of headache or blurred vision.

“These results indicate that the safety risks of sofpironium bromide can be considered small and controllable,” Dr. Fujimoto said. “Moreover, sofpironium bromide is a topical agent that patients can use by themselves, so it is highly convenient, unlike, say, botulinum toxin type A injections.”

Glycopyrronium bromide cream

Following on the heels of a recently published dose-ranging study (Br J Dermatol. 2020 Jan;182[1]:229-231), Dr. Abels presented the 4-week outcomes of a phase 3a, double-blind, randomized, five-country trial of once-daily 1% GPB cream or placebo in 171 patients with moderate or severe primary axillary hyperhidrosis. A phase 3b, open-label, 72-week, long-term safety trial is ongoing in 516 patients.

The primary endpoint of the 4-week trial was the reduction in gravimetric sweat production from day 1 to day 29. A reduction of 50% or more was documented in 57.5% of the patients on GBP and 34.5% of controls. A 75% or greater reduction occurred in 32.2% of the active-treatment group and 16.7% of those on placebo. And a decrease of at least 90% was seen in 23% of patients on topical GBP, compared with 9.5% of controls. All these between-group differences were significant.

The FDA now requires a quality of life measurement as a coprimary endpoint in phase 3 hyperhidrosis studies, and the phase 3 GBP trial also served as the successful validation study for a new patient-reported quality of life instrument designed specifically for this purpose. The new tool, known as the Hyperhydrosis Quality of Life questionnaire (HidroQol), proved much more sensitive than the HDSS or DLQI for evaluating clinical improvement in response to treatment (Br J Dermatol. 2020 Jun 8. doi: 10.1111/bjd.19300).

Initial results from the long-term phase 3b safety study should be available this fall on the first 100 patients followed on topical GBP for 1 year and for 300 followed for 6 months, Dr. Abels said.

Dr. Fujimoto reported serving as a paid consultant to and speaker for Kaken Pharmaceutical, which is developing SBP gel with Brickell Biotech. Dr. Abels is an employee of the company that is developing GPB cream.

[email protected]

Safe and effective new prescription topical therapies for primary axillary hyperhidrosis took a giant step closer to reaching clinical practice following positive reports from two phase 3, randomized, controlled trials of novel agents presented at the virtual annual meeting of the American Academy of Dermatology.

simarik/iStock/Getty Images

Both investigational topical anticholinergic agents – 5% sofpironium bromide (SPB) gel and 1% glycopyrronium bromide (GPB) cream – met all of the efficacy and safety endpoints required by the Food and Drug Administration.

Primary axillary hyperhidrosis, or symmetrical bilateral excessive armpit sweating, has a prevalence worldwide of 1%-16%, with 5%-6% the most frequently cited numbers. The condition has a strong adverse impact on quality of life. Primary axillary hyperhidrosis is not caused by a disorder of the sweat glands; rather, it’s actually a dysregulation of the autonomic nervous system leading to disproportionate sweating, explained Christoph Abels, MD, PhD, medical director at Dr. August Wolff in Bielefeld, Germany.

“What’s surprising is that more than 50% of patients do not receive appropriate treatment, very likely due to lack of awareness or embarrassment,” he added.

Also, many patients are put off by the systemic side effects of the oral anticholinergic agents, which are the current off-label treatment mainstay for patients with moderate or severe disease, according to Tomoko Fujimoto, MD, PhD, director of Ikebukuro Nishiguchi Fukurou Dermatology, near Tokyo.
 

Sofpironium bromide gel

Dr. Fujimoto presented the results of a phase 3, double-blind, multicenter, 6-week, vehicle-controlled clinical trial conducted in 281 Japanese patients with moderate to severe primary axillary hyperhidrosis as defined by a baseline score of 3 or 4 on the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Participants were randomized to self-application of 5% SPB gel or its vehicle once daily before bedtime.

Sofpironium bromide blocks the cholinergic response mediated by the M3 muscarinic receptor subtype expressed on eccrine sweat glands, thereby inhibiting sweating. The drug then undergoes breakdown into an inactive metabolite after reaching the blood.

An important aspect of both SPB gel and GPB cream is that these agents are rolled onto the axillae using a dedicated applicator. Patients never touch the medications with their hands, thus avoiding accidental exposure to the mucous membranes. This largely prevents problems with mydriasis and blurred vision as anticholinergic side effects, which has been an issue with glycopyrronium tosylate topical cloth wipes (Qbrexza), the first FDA-approved treatment for primary axillary hyperhidrosis.

The primary endpoint in the Japanese study was at least a 1-point improvement on the HDSS plus at least a 50% reduction in gravimetric sweat production between baseline and week 6. This composite outcome was achieved in 53.9% of patients in the active treatment arm, compared with 36.4% of controls.

The secondary endpoint consisting of a week-6 HDSS score of 1 or 2 – that is, underarm sweating that’s either never noticeable or is tolerable – occurred in 60.3% of the sofpironium bromide group and 47.9% of controls, a between-group difference that achieved statistical significance by week 2, when the rates were 46.8% and 28.2%.

The reduction in total gravimetric weight of axillary sweat from a mean baseline of 227 mg collected over 5 minutes was also significantly greater in the SPB group: a decrease of 157.6 mg, compared with 127.6 mg in controls; a between-group difference that also was significant by week 2. The mean Dermatology Life Quality Index score dropped by 6.8 points in the active-treatment arm from a baseline of 11.3, a significant improvement over the mean 4.5-point drop in controls.

A new 5-point measure of subjective symptoms of primary axillary hyperhidrosis – the Hyperhidrosis Disease Severity Measure–Axilla (HDSM-Ax) – improved by 1.41 points in the SPB group, significantly better than the 0.93 points in vehicle-treated controls. About 48% of patients on SBP experienced at least a 1.5-point reduction on the HDSM-Ax, compared with 26% of controls.

Regarding safety, there was a 2% incidence of application-site itch or scale in the SBP group. Anticholinergic side effects consisted of a single case of mydriasis, another of constipation, and two complaints of thirst, all mild, none resulting in treatment discontinuation. There were no reports of headache or blurred vision.

“These results indicate that the safety risks of sofpironium bromide can be considered small and controllable,” Dr. Fujimoto said. “Moreover, sofpironium bromide is a topical agent that patients can use by themselves, so it is highly convenient, unlike, say, botulinum toxin type A injections.”

Glycopyrronium bromide cream

Following on the heels of a recently published dose-ranging study (Br J Dermatol. 2020 Jan;182[1]:229-231), Dr. Abels presented the 4-week outcomes of a phase 3a, double-blind, randomized, five-country trial of once-daily 1% GPB cream or placebo in 171 patients with moderate or severe primary axillary hyperhidrosis. A phase 3b, open-label, 72-week, long-term safety trial is ongoing in 516 patients.

The primary endpoint of the 4-week trial was the reduction in gravimetric sweat production from day 1 to day 29. A reduction of 50% or more was documented in 57.5% of the patients on GBP and 34.5% of controls. A 75% or greater reduction occurred in 32.2% of the active-treatment group and 16.7% of those on placebo. And a decrease of at least 90% was seen in 23% of patients on topical GBP, compared with 9.5% of controls. All these between-group differences were significant.

The FDA now requires a quality of life measurement as a coprimary endpoint in phase 3 hyperhidrosis studies, and the phase 3 GBP trial also served as the successful validation study for a new patient-reported quality of life instrument designed specifically for this purpose. The new tool, known as the Hyperhydrosis Quality of Life questionnaire (HidroQol), proved much more sensitive than the HDSS or DLQI for evaluating clinical improvement in response to treatment (Br J Dermatol. 2020 Jun 8. doi: 10.1111/bjd.19300).

Initial results from the long-term phase 3b safety study should be available this fall on the first 100 patients followed on topical GBP for 1 year and for 300 followed for 6 months, Dr. Abels said.

Dr. Fujimoto reported serving as a paid consultant to and speaker for Kaken Pharmaceutical, which is developing SBP gel with Brickell Biotech. Dr. Abels is an employee of the company that is developing GPB cream.

[email protected]

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

When Virginia’s governor directed the postponement of all elective surgeries in late March, Wayne Batchelor, MD and his colleagues at the Inova Heart and Vascular Institute in Falls Church, Va., canceled about two-thirds of their transcatheter aortic valve replacement (TAVR) procedures.

Courtesy Wayne Batchelor, MD

They then categorized patients by tiers to gauge which procedures could safely be postponed and to guide triaging. And while they did not deviate from the practice of having both an interventional cardiologist and a cardiothoracic surgeon present for TAVR, they slimmed down preprocedural testing when feasible and delayed some 30-day post-TAVR echocardiographic assessments. “It was a delicate dance, very difficult dance. But luckily, we were able to navigate the challenges effectively,” said Dr. Batchelor, the institute’s director of interventional cardiology and interventional cardiology research.

A “system capacity dashboard” that merged bed and staffing data from interventional cardiology spaces with cardiovascular and noncardiovascular ICU beds, operating rooms, and other resources – and daily cross-department meetings – enabled them to proceed with the most urgent TAVR procedures while “keeping a buffer of ICU beds to accommodate an anticipated surge of COVID-19,” he explained.

Such adaptations in cardiac procedures and processes are occurring in hospitals across the country as efforts are made to minimize the risk of COVID-19 exposure for patients and staff. Dr. Batchelor is one of four cardiologists who shared their experiences and advice on common cardiac procedures across three locales: TAVR in Virginia, percutaneous coronary intervention (PCI) in New York City, and atrial fibrillation (AFib) ablation in Kentucky.
 

More on TAVR in Virginia

Inova’s framework for triaging structural heart disease interventions (largely TAVR and/or percutaneous mitral valve repair) comprised three tiers. Tier 1 captured “emergent cases that had to be done, no questions asked,” Dr. Batchelor said. For TAVR, these were inpatients with severe to critical symptomatic aortic stenosis and advanced congestive heart failure who could not safely be discharged, as well as other patients “with refractory symptoms of heart failure that were compelling.” Many had associated left ventricular systolic dysfunction.

Those who could delay 14-30 days were placed in tier 2, and patients who “we felt were fairly stable and could wait at least 30 days” were placed in tier 3. “For TAVR, a tier 3 patient might be the one … who has severe aortic stenosis but is walking around and doing well at home with only stable exertional symptoms,” he said.

Patients whose procedures were delayed were contacted weekly by the valve clinic’s advanced practice practitioners through video visits or telephone calls, and tier categorization was reevaluated if symptoms worsened. “We had to keep in close contact with them,” Dr. Batchelor said. “These patients can deteriorate quite rapidly and sometimes without much warning.”

Virtual video visits were often used for 30-day postprocedural follow-ups, taking the place of in-person visits during which post-TAVR echocardiographic assessments would normally be performed. “For follow-up, we’d often just do a quick visit to check the vascular access site within 7-10 days, and then, if they were doing okay we’d delay the 30-day echo to a later time frame,” he said.

Preprocedural testing was streamlined to minimize the number of patient-provider interactions, with pulmonary function testing and pre-TAVR catheterization omitted unless absolutely necessary. “A TAVR CT angiogram [performed within the prior year] is the only test you really absolutely need,” Dr. Batchelor said. “We were much less likely to order a heart catheterization unless the patient was having angina and high risk or suspicion for significant coronary artery disease.”

This approach was not associated with any compromise in postprocedural outcomes, he noted. Prior to the pandemic, Inova routinely employed a minimalist approach to TAVR with moderate conscious sedation and avoiding transesophageal echocardiography – steps that were recommended for structural heart procedures in the COVID-19 era in a published review by the heart team at New York-Presbyterian Hospital/Columbia University Irving Medical Center.

The New York review is useful for cardiologists in areas with rising case burdens of COVID-19, Dr. Batchelor said, as is a position statement he coauthored from the American College of Cardiology and the Society for Cardiology and Angiography Interventions (SCAI) on triage considerations for structural heart disease interventions during the pandemic.

TAVR’s resource-heavy nature made the “system capacity dashboard” and daily meetings critical, Dr. Batchelor explained. At one point during the hold on elective procedures, the Falls Church INOVA facility had approximately 300 patients with COVID-19, a significant proportion of whom were in cardiac ICU beds.

“Everyone has to be flexible and learn,” he said. “We trained our cardiologists on managing ventilators in case some of the [critical care] staff got ill or were overwhelmed by the surge.”

More than 2 months after the surge eased and the ban on elective surgery was lifted, Dr. Batchelor and his colleagues are still using the dashboard and continue to meet daily to discuss COVID-19 prevalence in the hospital and the community as they work through the backlog of delayed procedures. They also routinely review the status of COVID-19 testing for inpatients and outpatients and the donning and doffing of personal protective equipment.

“You have to communicate early and often across the whole system of care because you’re competing for the same resources,” he advised. “And you have to be flexible and reassess. A policy that works at the beginning of the pandemic might have to change.”
 

PCI in New York

Before the pandemic, the cardiac catheterization laboratory at Mount Sinai Morningside Hospital in New York handled a monthly average of 140-150 PCIs, including 6-10 primary PCIs for ST-segment elevation myocardial infarction.

Courtesy of Mount Sinai Morningside

When electives were halted by the hospital in March and the City became the global epicenter for COVID-19, the cath lab went quiet. “Even though we were still able to do urgent cases or emergent cases, the case volume dropped tremendously,” said Jacqueline E. Tamis-Holland, MD, associate director of the cardiac catheterization laboratory and director of the interventional cardiology fellowship. “There weren’t many outpatients in our hospital … and by late March and through April, there wasn’t a single acute infarction.”

She and Tak W. Kwan, MD, director of the cardiac catheterization laboratory and professor of medicine at Icahn School of Medicine at Mount Sinai, New York, were prepared to move true STEMI patients into the cath lab for primary PCI without delay unless the staff or system were overrun.

That primary PCI should remain the first-line treatment for STEMI even in cases of confirmed or suspected COVID-19 was recommended by SCAI guidance issued in March and by a consensus statement released by the SCAI, ACC, and American College of Emergency Physicians in April – and “we were very much of the same frame of mind,” Dr. Tamis-Holland said.

Deciding which elective cases could not be delayed required a completely individualized approach, the cardiologists emphasized. Dr. Tamis-Holland had a few patients scheduled for elective PCI when the hold began, and “we spoke every few days or once a week in the beginning, then transitioned to once every 2 weeks,” she said. “With medical therapy and given that they were relatively sedentary, my patients did okay [with the delays].”

For subsequent patients, she considered their symptoms or stress test results. “If it’s someone who I’d [normally] wait until next week to schedule the cath, then we would wait 2 or 3 more weeks, or a month more with careful monitoring,” she said. “Certainly, there was a decrease in the number of abnormal stress tests that I referred to the cath lab during [the surge period].”

Dr. Kwan described one patient who had new-onset congestive heart failure in late March “with a markedly positive nuclear stress test.” The patient was monitored with twice-weekly telemedicine visits and office visits, and a cardiac catheterization was performed in early May as an urgent elective case. “He had severe three-vessel and left main disease,” he said. “Subsequently, [coronary artery bypass surgery] was done.”

There were no changes in the PCI procedure itself in terms of hospital stay (most elective cases at Mt. Sinai are same-day procedures) or in staffing, other than a ban on visiting students or residents. The most important changes during the surge – in addition to stocking enough personal protective equipment – concerned testing. Patients undergoing elective PCI are tested for the novel coronavirus 72 hours before the procedure, and rapid testing is performed in the emergency room for STEMI patients to determine patient disposition after the procedure.

“Until we have the results back we should treat all patients as if they are a patient under investigation or have COVID,” said Dr. Tamis-Holland, who helped develop emergency guidance on STEMI systems of care during the pandemic for the American Heart Association.

In early May, the hospital freed up additional space for cardiac care, allowing more “urgent-elective” PCIs to be done. Some patients were reluctant to proceed, the cardiologists said, because of a no-visitor policy. In mid-June, the hold on elective procedures was lifted, and around the same time, the hospital shifted to a one-visitor policy. Still, some patients opted to continue longer with medical therapy.

Patients need to feel comfortable, and “there is a lag time from the time everything opens up and when patients get their stress tests and their evaluations, and then arrive for PCI,” said Dr. Tamis-Holland.

By mid-July, the cardiologists were anticipating an increase in complications from infarctions among patients who “waited them out at home” – heart failure or mitral valve regurgitation, for instance – but, in their hospital at least, “we haven’t really seen that,” she added.
 

AFib ablation in Kentucky

As New York experienced its surge, John Mandrola, MD, and other electrophysiologists across the Baptist Health system in Kentucky reached a consensus on how to categorize their procedures. Electrophysiology interventions were classified urgent, emergent, and truly elective in the event that the state’s relatively low case burden of COVID-19 were to significantly worsen.

There was no doubt where AFib ablation sat. “It’s one of the most elective procedures there is” in terms of scheduling under normal circumstances, and it almost always requires an overnight stay and general anesthesia – factors that upped the ante on an elective classification, said Dr. Mandrola.

All AF ablations were deemed elective unless the patient required immediate hospitalization. For 8-10 weeks during the state’s shutdown of elective care, Dr. Mandrola and his partner successfully monitored patients with phone calls. “To be honest,” he said, “most patients did not want to have their AFib ablation anyway until the pandemic slowed and they knew it was safe.”

In some cases, patients reported that their symptoms were improving: “There are so many things to speculate about. ... Was it that everyone took their foot off the accelerator?” Dr. Mandrola thinks that postpandemic outcomes analyses may drive more scrutiny of the necessity of some AFib ablations and other procedures and tests. AFib ablation “has its place but is probably overused,” he said.

During the pause on electives, “the vast majority of procedures we did were pacemaker procedures,” he said. “We also did some atrial flutter ablations, and ablations for ventricular tachycardia and supraventricular tachycardia.” In mid-July, as the COVID-19 case burden in Kentucky remained relatively low, Dr. Mandrola was “up to 120%” of his pre-COVID electrophysiology volume – but ready to scale back again if needed.

Dr. Batchelor reported consulting fees from Boston Scientific, Abbott Medical, Medtronic, and V-wave. Dr. Kwan, Dr. Mandrola, and Dr. Tamis-Holland reported no relevant financial disclosures.
 

This article is a collaboration between Medscape and MDedge. A version of it originally appeared on Medscape.com.

When Virginia’s governor directed the postponement of all elective surgeries in late March, Wayne Batchelor, MD and his colleagues at the Inova Heart and Vascular Institute in Falls Church, Va., canceled about two-thirds of their transcatheter aortic valve replacement (TAVR) procedures.

Courtesy Wayne Batchelor, MD

They then categorized patients by tiers to gauge which procedures could safely be postponed and to guide triaging. And while they did not deviate from the practice of having both an interventional cardiologist and a cardiothoracic surgeon present for TAVR, they slimmed down preprocedural testing when feasible and delayed some 30-day post-TAVR echocardiographic assessments. “It was a delicate dance, very difficult dance. But luckily, we were able to navigate the challenges effectively,” said Dr. Batchelor, the institute’s director of interventional cardiology and interventional cardiology research.

A “system capacity dashboard” that merged bed and staffing data from interventional cardiology spaces with cardiovascular and noncardiovascular ICU beds, operating rooms, and other resources – and daily cross-department meetings – enabled them to proceed with the most urgent TAVR procedures while “keeping a buffer of ICU beds to accommodate an anticipated surge of COVID-19,” he explained.

Such adaptations in cardiac procedures and processes are occurring in hospitals across the country as efforts are made to minimize the risk of COVID-19 exposure for patients and staff. Dr. Batchelor is one of four cardiologists who shared their experiences and advice on common cardiac procedures across three locales: TAVR in Virginia, percutaneous coronary intervention (PCI) in New York City, and atrial fibrillation (AFib) ablation in Kentucky.
 

More on TAVR in Virginia

Inova’s framework for triaging structural heart disease interventions (largely TAVR and/or percutaneous mitral valve repair) comprised three tiers. Tier 1 captured “emergent cases that had to be done, no questions asked,” Dr. Batchelor said. For TAVR, these were inpatients with severe to critical symptomatic aortic stenosis and advanced congestive heart failure who could not safely be discharged, as well as other patients “with refractory symptoms of heart failure that were compelling.” Many had associated left ventricular systolic dysfunction.

Those who could delay 14-30 days were placed in tier 2, and patients who “we felt were fairly stable and could wait at least 30 days” were placed in tier 3. “For TAVR, a tier 3 patient might be the one … who has severe aortic stenosis but is walking around and doing well at home with only stable exertional symptoms,” he said.

Patients whose procedures were delayed were contacted weekly by the valve clinic’s advanced practice practitioners through video visits or telephone calls, and tier categorization was reevaluated if symptoms worsened. “We had to keep in close contact with them,” Dr. Batchelor said. “These patients can deteriorate quite rapidly and sometimes without much warning.”

Virtual video visits were often used for 30-day postprocedural follow-ups, taking the place of in-person visits during which post-TAVR echocardiographic assessments would normally be performed. “For follow-up, we’d often just do a quick visit to check the vascular access site within 7-10 days, and then, if they were doing okay we’d delay the 30-day echo to a later time frame,” he said.

Preprocedural testing was streamlined to minimize the number of patient-provider interactions, with pulmonary function testing and pre-TAVR catheterization omitted unless absolutely necessary. “A TAVR CT angiogram [performed within the prior year] is the only test you really absolutely need,” Dr. Batchelor said. “We were much less likely to order a heart catheterization unless the patient was having angina and high risk or suspicion for significant coronary artery disease.”

This approach was not associated with any compromise in postprocedural outcomes, he noted. Prior to the pandemic, Inova routinely employed a minimalist approach to TAVR with moderate conscious sedation and avoiding transesophageal echocardiography – steps that were recommended for structural heart procedures in the COVID-19 era in a published review by the heart team at New York-Presbyterian Hospital/Columbia University Irving Medical Center.

The New York review is useful for cardiologists in areas with rising case burdens of COVID-19, Dr. Batchelor said, as is a position statement he coauthored from the American College of Cardiology and the Society for Cardiology and Angiography Interventions (SCAI) on triage considerations for structural heart disease interventions during the pandemic.

TAVR’s resource-heavy nature made the “system capacity dashboard” and daily meetings critical, Dr. Batchelor explained. At one point during the hold on elective procedures, the Falls Church INOVA facility had approximately 300 patients with COVID-19, a significant proportion of whom were in cardiac ICU beds.

“Everyone has to be flexible and learn,” he said. “We trained our cardiologists on managing ventilators in case some of the [critical care] staff got ill or were overwhelmed by the surge.”

More than 2 months after the surge eased and the ban on elective surgery was lifted, Dr. Batchelor and his colleagues are still using the dashboard and continue to meet daily to discuss COVID-19 prevalence in the hospital and the community as they work through the backlog of delayed procedures. They also routinely review the status of COVID-19 testing for inpatients and outpatients and the donning and doffing of personal protective equipment.

“You have to communicate early and often across the whole system of care because you’re competing for the same resources,” he advised. “And you have to be flexible and reassess. A policy that works at the beginning of the pandemic might have to change.”
 

PCI in New York

Before the pandemic, the cardiac catheterization laboratory at Mount Sinai Morningside Hospital in New York handled a monthly average of 140-150 PCIs, including 6-10 primary PCIs for ST-segment elevation myocardial infarction.

Courtesy of Mount Sinai Morningside

When electives were halted by the hospital in March and the City became the global epicenter for COVID-19, the cath lab went quiet. “Even though we were still able to do urgent cases or emergent cases, the case volume dropped tremendously,” said Jacqueline E. Tamis-Holland, MD, associate director of the cardiac catheterization laboratory and director of the interventional cardiology fellowship. “There weren’t many outpatients in our hospital … and by late March and through April, there wasn’t a single acute infarction.”

She and Tak W. Kwan, MD, director of the cardiac catheterization laboratory and professor of medicine at Icahn School of Medicine at Mount Sinai, New York, were prepared to move true STEMI patients into the cath lab for primary PCI without delay unless the staff or system were overrun.

That primary PCI should remain the first-line treatment for STEMI even in cases of confirmed or suspected COVID-19 was recommended by SCAI guidance issued in March and by a consensus statement released by the SCAI, ACC, and American College of Emergency Physicians in April – and “we were very much of the same frame of mind,” Dr. Tamis-Holland said.

Deciding which elective cases could not be delayed required a completely individualized approach, the cardiologists emphasized. Dr. Tamis-Holland had a few patients scheduled for elective PCI when the hold began, and “we spoke every few days or once a week in the beginning, then transitioned to once every 2 weeks,” she said. “With medical therapy and given that they were relatively sedentary, my patients did okay [with the delays].”

For subsequent patients, she considered their symptoms or stress test results. “If it’s someone who I’d [normally] wait until next week to schedule the cath, then we would wait 2 or 3 more weeks, or a month more with careful monitoring,” she said. “Certainly, there was a decrease in the number of abnormal stress tests that I referred to the cath lab during [the surge period].”

Dr. Kwan described one patient who had new-onset congestive heart failure in late March “with a markedly positive nuclear stress test.” The patient was monitored with twice-weekly telemedicine visits and office visits, and a cardiac catheterization was performed in early May as an urgent elective case. “He had severe three-vessel and left main disease,” he said. “Subsequently, [coronary artery bypass surgery] was done.”

There were no changes in the PCI procedure itself in terms of hospital stay (most elective cases at Mt. Sinai are same-day procedures) or in staffing, other than a ban on visiting students or residents. The most important changes during the surge – in addition to stocking enough personal protective equipment – concerned testing. Patients undergoing elective PCI are tested for the novel coronavirus 72 hours before the procedure, and rapid testing is performed in the emergency room for STEMI patients to determine patient disposition after the procedure.

“Until we have the results back we should treat all patients as if they are a patient under investigation or have COVID,” said Dr. Tamis-Holland, who helped develop emergency guidance on STEMI systems of care during the pandemic for the American Heart Association.

In early May, the hospital freed up additional space for cardiac care, allowing more “urgent-elective” PCIs to be done. Some patients were reluctant to proceed, the cardiologists said, because of a no-visitor policy. In mid-June, the hold on elective procedures was lifted, and around the same time, the hospital shifted to a one-visitor policy. Still, some patients opted to continue longer with medical therapy.

Patients need to feel comfortable, and “there is a lag time from the time everything opens up and when patients get their stress tests and their evaluations, and then arrive for PCI,” said Dr. Tamis-Holland.

By mid-July, the cardiologists were anticipating an increase in complications from infarctions among patients who “waited them out at home” – heart failure or mitral valve regurgitation, for instance – but, in their hospital at least, “we haven’t really seen that,” she added.
 

AFib ablation in Kentucky

As New York experienced its surge, John Mandrola, MD, and other electrophysiologists across the Baptist Health system in Kentucky reached a consensus on how to categorize their procedures. Electrophysiology interventions were classified urgent, emergent, and truly elective in the event that the state’s relatively low case burden of COVID-19 were to significantly worsen.

There was no doubt where AFib ablation sat. “It’s one of the most elective procedures there is” in terms of scheduling under normal circumstances, and it almost always requires an overnight stay and general anesthesia – factors that upped the ante on an elective classification, said Dr. Mandrola.

All AF ablations were deemed elective unless the patient required immediate hospitalization. For 8-10 weeks during the state’s shutdown of elective care, Dr. Mandrola and his partner successfully monitored patients with phone calls. “To be honest,” he said, “most patients did not want to have their AFib ablation anyway until the pandemic slowed and they knew it was safe.”

In some cases, patients reported that their symptoms were improving: “There are so many things to speculate about. ... Was it that everyone took their foot off the accelerator?” Dr. Mandrola thinks that postpandemic outcomes analyses may drive more scrutiny of the necessity of some AFib ablations and other procedures and tests. AFib ablation “has its place but is probably overused,” he said.

During the pause on electives, “the vast majority of procedures we did were pacemaker procedures,” he said. “We also did some atrial flutter ablations, and ablations for ventricular tachycardia and supraventricular tachycardia.” In mid-July, as the COVID-19 case burden in Kentucky remained relatively low, Dr. Mandrola was “up to 120%” of his pre-COVID electrophysiology volume – but ready to scale back again if needed.

Dr. Batchelor reported consulting fees from Boston Scientific, Abbott Medical, Medtronic, and V-wave. Dr. Kwan, Dr. Mandrola, and Dr. Tamis-Holland reported no relevant financial disclosures.
 

This article is a collaboration between Medscape and MDedge. A version of it originally appeared on Medscape.com.

When Virginia’s governor directed the postponement of all elective surgeries in late March, Wayne Batchelor, MD and his colleagues at the Inova Heart and Vascular Institute in Falls Church, Va., canceled about two-thirds of their transcatheter aortic valve replacement (TAVR) procedures.

Courtesy Wayne Batchelor, MD

They then categorized patients by tiers to gauge which procedures could safely be postponed and to guide triaging. And while they did not deviate from the practice of having both an interventional cardiologist and a cardiothoracic surgeon present for TAVR, they slimmed down preprocedural testing when feasible and delayed some 30-day post-TAVR echocardiographic assessments. “It was a delicate dance, very difficult dance. But luckily, we were able to navigate the challenges effectively,” said Dr. Batchelor, the institute’s director of interventional cardiology and interventional cardiology research.

A “system capacity dashboard” that merged bed and staffing data from interventional cardiology spaces with cardiovascular and noncardiovascular ICU beds, operating rooms, and other resources – and daily cross-department meetings – enabled them to proceed with the most urgent TAVR procedures while “keeping a buffer of ICU beds to accommodate an anticipated surge of COVID-19,” he explained.

Such adaptations in cardiac procedures and processes are occurring in hospitals across the country as efforts are made to minimize the risk of COVID-19 exposure for patients and staff. Dr. Batchelor is one of four cardiologists who shared their experiences and advice on common cardiac procedures across three locales: TAVR in Virginia, percutaneous coronary intervention (PCI) in New York City, and atrial fibrillation (AFib) ablation in Kentucky.
 

More on TAVR in Virginia

Inova’s framework for triaging structural heart disease interventions (largely TAVR and/or percutaneous mitral valve repair) comprised three tiers. Tier 1 captured “emergent cases that had to be done, no questions asked,” Dr. Batchelor said. For TAVR, these were inpatients with severe to critical symptomatic aortic stenosis and advanced congestive heart failure who could not safely be discharged, as well as other patients “with refractory symptoms of heart failure that were compelling.” Many had associated left ventricular systolic dysfunction.

Those who could delay 14-30 days were placed in tier 2, and patients who “we felt were fairly stable and could wait at least 30 days” were placed in tier 3. “For TAVR, a tier 3 patient might be the one … who has severe aortic stenosis but is walking around and doing well at home with only stable exertional symptoms,” he said.

Patients whose procedures were delayed were contacted weekly by the valve clinic’s advanced practice practitioners through video visits or telephone calls, and tier categorization was reevaluated if symptoms worsened. “We had to keep in close contact with them,” Dr. Batchelor said. “These patients can deteriorate quite rapidly and sometimes without much warning.”

Virtual video visits were often used for 30-day postprocedural follow-ups, taking the place of in-person visits during which post-TAVR echocardiographic assessments would normally be performed. “For follow-up, we’d often just do a quick visit to check the vascular access site within 7-10 days, and then, if they were doing okay we’d delay the 30-day echo to a later time frame,” he said.

Preprocedural testing was streamlined to minimize the number of patient-provider interactions, with pulmonary function testing and pre-TAVR catheterization omitted unless absolutely necessary. “A TAVR CT angiogram [performed within the prior year] is the only test you really absolutely need,” Dr. Batchelor said. “We were much less likely to order a heart catheterization unless the patient was having angina and high risk or suspicion for significant coronary artery disease.”

This approach was not associated with any compromise in postprocedural outcomes, he noted. Prior to the pandemic, Inova routinely employed a minimalist approach to TAVR with moderate conscious sedation and avoiding transesophageal echocardiography – steps that were recommended for structural heart procedures in the COVID-19 era in a published review by the heart team at New York-Presbyterian Hospital/Columbia University Irving Medical Center.

The New York review is useful for cardiologists in areas with rising case burdens of COVID-19, Dr. Batchelor said, as is a position statement he coauthored from the American College of Cardiology and the Society for Cardiology and Angiography Interventions (SCAI) on triage considerations for structural heart disease interventions during the pandemic.

TAVR’s resource-heavy nature made the “system capacity dashboard” and daily meetings critical, Dr. Batchelor explained. At one point during the hold on elective procedures, the Falls Church INOVA facility had approximately 300 patients with COVID-19, a significant proportion of whom were in cardiac ICU beds.

“Everyone has to be flexible and learn,” he said. “We trained our cardiologists on managing ventilators in case some of the [critical care] staff got ill or were overwhelmed by the surge.”

More than 2 months after the surge eased and the ban on elective surgery was lifted, Dr. Batchelor and his colleagues are still using the dashboard and continue to meet daily to discuss COVID-19 prevalence in the hospital and the community as they work through the backlog of delayed procedures. They also routinely review the status of COVID-19 testing for inpatients and outpatients and the donning and doffing of personal protective equipment.

“You have to communicate early and often across the whole system of care because you’re competing for the same resources,” he advised. “And you have to be flexible and reassess. A policy that works at the beginning of the pandemic might have to change.”
 

PCI in New York

Before the pandemic, the cardiac catheterization laboratory at Mount Sinai Morningside Hospital in New York handled a monthly average of 140-150 PCIs, including 6-10 primary PCIs for ST-segment elevation myocardial infarction.

Courtesy of Mount Sinai Morningside

When electives were halted by the hospital in March and the City became the global epicenter for COVID-19, the cath lab went quiet. “Even though we were still able to do urgent cases or emergent cases, the case volume dropped tremendously,” said Jacqueline E. Tamis-Holland, MD, associate director of the cardiac catheterization laboratory and director of the interventional cardiology fellowship. “There weren’t many outpatients in our hospital … and by late March and through April, there wasn’t a single acute infarction.”

She and Tak W. Kwan, MD, director of the cardiac catheterization laboratory and professor of medicine at Icahn School of Medicine at Mount Sinai, New York, were prepared to move true STEMI patients into the cath lab for primary PCI without delay unless the staff or system were overrun.

That primary PCI should remain the first-line treatment for STEMI even in cases of confirmed or suspected COVID-19 was recommended by SCAI guidance issued in March and by a consensus statement released by the SCAI, ACC, and American College of Emergency Physicians in April – and “we were very much of the same frame of mind,” Dr. Tamis-Holland said.

Deciding which elective cases could not be delayed required a completely individualized approach, the cardiologists emphasized. Dr. Tamis-Holland had a few patients scheduled for elective PCI when the hold began, and “we spoke every few days or once a week in the beginning, then transitioned to once every 2 weeks,” she said. “With medical therapy and given that they were relatively sedentary, my patients did okay [with the delays].”

For subsequent patients, she considered their symptoms or stress test results. “If it’s someone who I’d [normally] wait until next week to schedule the cath, then we would wait 2 or 3 more weeks, or a month more with careful monitoring,” she said. “Certainly, there was a decrease in the number of abnormal stress tests that I referred to the cath lab during [the surge period].”

Dr. Kwan described one patient who had new-onset congestive heart failure in late March “with a markedly positive nuclear stress test.” The patient was monitored with twice-weekly telemedicine visits and office visits, and a cardiac catheterization was performed in early May as an urgent elective case. “He had severe three-vessel and left main disease,” he said. “Subsequently, [coronary artery bypass surgery] was done.”

There were no changes in the PCI procedure itself in terms of hospital stay (most elective cases at Mt. Sinai are same-day procedures) or in staffing, other than a ban on visiting students or residents. The most important changes during the surge – in addition to stocking enough personal protective equipment – concerned testing. Patients undergoing elective PCI are tested for the novel coronavirus 72 hours before the procedure, and rapid testing is performed in the emergency room for STEMI patients to determine patient disposition after the procedure.

“Until we have the results back we should treat all patients as if they are a patient under investigation or have COVID,” said Dr. Tamis-Holland, who helped develop emergency guidance on STEMI systems of care during the pandemic for the American Heart Association.

In early May, the hospital freed up additional space for cardiac care, allowing more “urgent-elective” PCIs to be done. Some patients were reluctant to proceed, the cardiologists said, because of a no-visitor policy. In mid-June, the hold on elective procedures was lifted, and around the same time, the hospital shifted to a one-visitor policy. Still, some patients opted to continue longer with medical therapy.

Patients need to feel comfortable, and “there is a lag time from the time everything opens up and when patients get their stress tests and their evaluations, and then arrive for PCI,” said Dr. Tamis-Holland.

By mid-July, the cardiologists were anticipating an increase in complications from infarctions among patients who “waited them out at home” – heart failure or mitral valve regurgitation, for instance – but, in their hospital at least, “we haven’t really seen that,” she added.
 

AFib ablation in Kentucky

As New York experienced its surge, John Mandrola, MD, and other electrophysiologists across the Baptist Health system in Kentucky reached a consensus on how to categorize their procedures. Electrophysiology interventions were classified urgent, emergent, and truly elective in the event that the state’s relatively low case burden of COVID-19 were to significantly worsen.

There was no doubt where AFib ablation sat. “It’s one of the most elective procedures there is” in terms of scheduling under normal circumstances, and it almost always requires an overnight stay and general anesthesia – factors that upped the ante on an elective classification, said Dr. Mandrola.

All AF ablations were deemed elective unless the patient required immediate hospitalization. For 8-10 weeks during the state’s shutdown of elective care, Dr. Mandrola and his partner successfully monitored patients with phone calls. “To be honest,” he said, “most patients did not want to have their AFib ablation anyway until the pandemic slowed and they knew it was safe.”

In some cases, patients reported that their symptoms were improving: “There are so many things to speculate about. ... Was it that everyone took their foot off the accelerator?” Dr. Mandrola thinks that postpandemic outcomes analyses may drive more scrutiny of the necessity of some AFib ablations and other procedures and tests. AFib ablation “has its place but is probably overused,” he said.

During the pause on electives, “the vast majority of procedures we did were pacemaker procedures,” he said. “We also did some atrial flutter ablations, and ablations for ventricular tachycardia and supraventricular tachycardia.” In mid-July, as the COVID-19 case burden in Kentucky remained relatively low, Dr. Mandrola was “up to 120%” of his pre-COVID electrophysiology volume – but ready to scale back again if needed.

Dr. Batchelor reported consulting fees from Boston Scientific, Abbott Medical, Medtronic, and V-wave. Dr. Kwan, Dr. Mandrola, and Dr. Tamis-Holland reported no relevant financial disclosures.
 

This article is a collaboration between Medscape and MDedge. A version of it originally appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In individuals with inflammatory bowel disease and primary sclerosing cholangitis, younger age at diagnosis, male sex, and Afro-Caribbean heritage were significant risk factors for liver transplantation and disease-related death, based on a 10-year prospective population-based study.

These factors should be incorporated into the design of clinical trials, models for predicting disease, and studies of prognostic biomarkers for primary sclerosing cholangitis, Palak T. Trivedi, MBBS, MRCP, of the Universty of Birmingham (England) wrote with his associates in Gastroenterology.

The researchers identified newly diagnosed cases from a national health care registry in England between 2006 and 2016 (data on outcomes were collected through mid-2019). In all, 284,560 individuals had a new diagnosis of inflammatory bowel disease, among whom 2,588 also had primary sclerosing cholangitis. The investigators tracked deaths, liver transplantation, colonic resection, cholecystectomy, and diagnoses of colorectal cancer, cholangiosarcoma, and cancers of the pancreas, gallbladder, and liver. They evaluated rates of these outcomes among individuals with both primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD) and those with IBD only.

After controlling for sex, race, socioeconomic level, comorbidities, and older age, the researchers found that both men and women with PSC-IBD had a significantly greater risk for all-cause mortality, compared with individuals with IBD alone (hazard ratio, 3.20; 95% confidence interval, 3.01-3.40; P less than .001). Strikingly, individuals who were diagnosed with PSC when they were younger than 40 years had a more than sevenfold higher rate of all-cause mortality, compared with individuals with IBD only. In contrast, the incidence rate ratio for individuals diagnosed with PSC when they were older than 60 years was less than 1.5, compared with IBD-only individuals.

Having PSC and ulcerative colitis, being younger when diagnosed with PSC, and being of Afro-Carribean heritage all correlated with higher incidence of liver transplantation or death related to PSC. Individuals with PSC-IBD who were of Afro-Caribbean heritage had an approximately twofold greater risk for liver transplantation or PSC-related death compared with Whites (adjusted HR, 2.05; 95% CI, 1.14-3.70; P = .016). In contrast, women with PSC-IBD were at significantly lower risk for liver transplantation or disease-related death than were men (adjusted HR, 0.74; 95% CI, 0.57-0.97; P = .026).

“The onset of PSC confers heightened risks of all hepatobiliary malignancies, although annual imaging surveillance may associate with a reduced risk of cancer-related death,” the investigators found. Among patients with hepatobiliary cancer, annual imaging was associated with a twofold decrease in risk for cancer-related death (HR, 0.43; 95% CI, 0.23-0.80; P = .037).

Colorectal cancer tended to occur at a younger age among individuals with PSC-IBD, compared with those with IBD alone (median ages at diagnosis, 59 vs. 69 years; P less than .001). Notably, individuals with PSC diagnosed under age 50 years had about a fivefold higher incidence of colorectal cancer than did those with IBD alone, while those diagnosed at older ages had only about a twofold increase. With regard to colectomy, men diagnosed with PSC at younger ages were at the greatest risk, compared with women or individuals diagnosed after age 50 years. Individuals with ulcerative colitis and PSC had a 40% greater risk for colectomy risk than did IBD-only individuals (time-dependent adjusted HR, 1.65; 95% CI, 1.45-1.85; P less than .001).

“Whilst all-cause mortality rates increase with age, younger patients [with PSC] show a disproportionately increased incidence of liver transplantation, PSC-related death, and colorectal cancer,” the researchers concluded. “Consideration of age at diagnosis should therefore be applied in the stratification of patients for future clinical trials, disease prediction models, and prognostic biomarker discovery.”

Dr. Trivedi disclosed support from the National Institute for Health Research Birmingham Biomedical Research Centre, at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. No other disclosures were reported.

SOURCE: Trivedi PJ et al. Gastroenterology. 2020 May 19. doi: 10.1053/j.gastro.2020.05.049.
 

In individuals with inflammatory bowel disease and primary sclerosing cholangitis, younger age at diagnosis, male sex, and Afro-Caribbean heritage were significant risk factors for liver transplantation and disease-related death, based on a 10-year prospective population-based study.

These factors should be incorporated into the design of clinical trials, models for predicting disease, and studies of prognostic biomarkers for primary sclerosing cholangitis, Palak T. Trivedi, MBBS, MRCP, of the Universty of Birmingham (England) wrote with his associates in Gastroenterology.

The researchers identified newly diagnosed cases from a national health care registry in England between 2006 and 2016 (data on outcomes were collected through mid-2019). In all, 284,560 individuals had a new diagnosis of inflammatory bowel disease, among whom 2,588 also had primary sclerosing cholangitis. The investigators tracked deaths, liver transplantation, colonic resection, cholecystectomy, and diagnoses of colorectal cancer, cholangiosarcoma, and cancers of the pancreas, gallbladder, and liver. They evaluated rates of these outcomes among individuals with both primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD) and those with IBD only.

After controlling for sex, race, socioeconomic level, comorbidities, and older age, the researchers found that both men and women with PSC-IBD had a significantly greater risk for all-cause mortality, compared with individuals with IBD alone (hazard ratio, 3.20; 95% confidence interval, 3.01-3.40; P less than .001). Strikingly, individuals who were diagnosed with PSC when they were younger than 40 years had a more than sevenfold higher rate of all-cause mortality, compared with individuals with IBD only. In contrast, the incidence rate ratio for individuals diagnosed with PSC when they were older than 60 years was less than 1.5, compared with IBD-only individuals.

Having PSC and ulcerative colitis, being younger when diagnosed with PSC, and being of Afro-Carribean heritage all correlated with higher incidence of liver transplantation or death related to PSC. Individuals with PSC-IBD who were of Afro-Caribbean heritage had an approximately twofold greater risk for liver transplantation or PSC-related death compared with Whites (adjusted HR, 2.05; 95% CI, 1.14-3.70; P = .016). In contrast, women with PSC-IBD were at significantly lower risk for liver transplantation or disease-related death than were men (adjusted HR, 0.74; 95% CI, 0.57-0.97; P = .026).

“The onset of PSC confers heightened risks of all hepatobiliary malignancies, although annual imaging surveillance may associate with a reduced risk of cancer-related death,” the investigators found. Among patients with hepatobiliary cancer, annual imaging was associated with a twofold decrease in risk for cancer-related death (HR, 0.43; 95% CI, 0.23-0.80; P = .037).

Colorectal cancer tended to occur at a younger age among individuals with PSC-IBD, compared with those with IBD alone (median ages at diagnosis, 59 vs. 69 years; P less than .001). Notably, individuals with PSC diagnosed under age 50 years had about a fivefold higher incidence of colorectal cancer than did those with IBD alone, while those diagnosed at older ages had only about a twofold increase. With regard to colectomy, men diagnosed with PSC at younger ages were at the greatest risk, compared with women or individuals diagnosed after age 50 years. Individuals with ulcerative colitis and PSC had a 40% greater risk for colectomy risk than did IBD-only individuals (time-dependent adjusted HR, 1.65; 95% CI, 1.45-1.85; P less than .001).

“Whilst all-cause mortality rates increase with age, younger patients [with PSC] show a disproportionately increased incidence of liver transplantation, PSC-related death, and colorectal cancer,” the researchers concluded. “Consideration of age at diagnosis should therefore be applied in the stratification of patients for future clinical trials, disease prediction models, and prognostic biomarker discovery.”

Dr. Trivedi disclosed support from the National Institute for Health Research Birmingham Biomedical Research Centre, at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. No other disclosures were reported.

SOURCE: Trivedi PJ et al. Gastroenterology. 2020 May 19. doi: 10.1053/j.gastro.2020.05.049.
 

In individuals with inflammatory bowel disease and primary sclerosing cholangitis, younger age at diagnosis, male sex, and Afro-Caribbean heritage were significant risk factors for liver transplantation and disease-related death, based on a 10-year prospective population-based study.

These factors should be incorporated into the design of clinical trials, models for predicting disease, and studies of prognostic biomarkers for primary sclerosing cholangitis, Palak T. Trivedi, MBBS, MRCP, of the Universty of Birmingham (England) wrote with his associates in Gastroenterology.

The researchers identified newly diagnosed cases from a national health care registry in England between 2006 and 2016 (data on outcomes were collected through mid-2019). In all, 284,560 individuals had a new diagnosis of inflammatory bowel disease, among whom 2,588 also had primary sclerosing cholangitis. The investigators tracked deaths, liver transplantation, colonic resection, cholecystectomy, and diagnoses of colorectal cancer, cholangiosarcoma, and cancers of the pancreas, gallbladder, and liver. They evaluated rates of these outcomes among individuals with both primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD) and those with IBD only.

After controlling for sex, race, socioeconomic level, comorbidities, and older age, the researchers found that both men and women with PSC-IBD had a significantly greater risk for all-cause mortality, compared with individuals with IBD alone (hazard ratio, 3.20; 95% confidence interval, 3.01-3.40; P less than .001). Strikingly, individuals who were diagnosed with PSC when they were younger than 40 years had a more than sevenfold higher rate of all-cause mortality, compared with individuals with IBD only. In contrast, the incidence rate ratio for individuals diagnosed with PSC when they were older than 60 years was less than 1.5, compared with IBD-only individuals.

Having PSC and ulcerative colitis, being younger when diagnosed with PSC, and being of Afro-Carribean heritage all correlated with higher incidence of liver transplantation or death related to PSC. Individuals with PSC-IBD who were of Afro-Caribbean heritage had an approximately twofold greater risk for liver transplantation or PSC-related death compared with Whites (adjusted HR, 2.05; 95% CI, 1.14-3.70; P = .016). In contrast, women with PSC-IBD were at significantly lower risk for liver transplantation or disease-related death than were men (adjusted HR, 0.74; 95% CI, 0.57-0.97; P = .026).

“The onset of PSC confers heightened risks of all hepatobiliary malignancies, although annual imaging surveillance may associate with a reduced risk of cancer-related death,” the investigators found. Among patients with hepatobiliary cancer, annual imaging was associated with a twofold decrease in risk for cancer-related death (HR, 0.43; 95% CI, 0.23-0.80; P = .037).

Colorectal cancer tended to occur at a younger age among individuals with PSC-IBD, compared with those with IBD alone (median ages at diagnosis, 59 vs. 69 years; P less than .001). Notably, individuals with PSC diagnosed under age 50 years had about a fivefold higher incidence of colorectal cancer than did those with IBD alone, while those diagnosed at older ages had only about a twofold increase. With regard to colectomy, men diagnosed with PSC at younger ages were at the greatest risk, compared with women or individuals diagnosed after age 50 years. Individuals with ulcerative colitis and PSC had a 40% greater risk for colectomy risk than did IBD-only individuals (time-dependent adjusted HR, 1.65; 95% CI, 1.45-1.85; P less than .001).

“Whilst all-cause mortality rates increase with age, younger patients [with PSC] show a disproportionately increased incidence of liver transplantation, PSC-related death, and colorectal cancer,” the researchers concluded. “Consideration of age at diagnosis should therefore be applied in the stratification of patients for future clinical trials, disease prediction models, and prognostic biomarker discovery.”

Dr. Trivedi disclosed support from the National Institute for Health Research Birmingham Biomedical Research Centre, at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. No other disclosures were reported.

SOURCE: Trivedi PJ et al. Gastroenterology. 2020 May 19. doi: 10.1053/j.gastro.2020.05.049.
 

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Adam B. Hill, MD, is home on a “staycation” this week. Today, he took a 3-hour nap. I know this because I follow Dr. Hill on Twitter, where he has an active feed, a lot of posts, retweets, and more than 20,000 followers.

I also know from Twitter that he is married and has three young children, that he was once suicidal, and has been treated for major depression and alcoholism. As a palliative care doctor, Dr. Hill was required by his state medical board to blow into a breathalyzer several times a day for 5 years – something he felt quite shamed by – and while I’ve never met him, I felt just a little bit proud of this stranger when he was released from the medical board’s oversight.

Dr. Hill’s memoir, “Long Walk Out of the Woods: A Physician’s Story of Addiction, Depression, Hope, and Recovery” (Central Recovery Press, 2019) is the culmination of his efforts to use his difficulties as a way of offering hope and connection to anyone who struggled as he has, or to anyone who has struggled at all. Like his Twitter feed, it is a display of vulnerability and gratitude by someone who has been through dark times then returned to conquer his monsters.

Courtesy Central Recovery Press

He begins by setting the stage for us. “My name is Adam,” he announces in the preface. He tells us his various titles: human being, husband, father, physician, recovering alcoholic, and psychiatric patient. “In the midst of these struggles, working in modern medicine fractured my identity, stole my authenticity, and left me a shell of the person I wanted to be.”

We learn that he tried to buy a gun, but there was a waiting period and he could not purchase the firearm. Instead, he walked into the woods to drink himself to death, with sleeping pills as an add-on – obviously, he didn’t die, and his journey back from his failed suicidal mission is the meat of the book.

Dr. Hill was a quiet and timid child, and he was bullied at school in a way that has lingered on. He struggles with perfectionism and with a sense of never quite belonging. He was a good student, and later a competitive tennis player who was destined for a regional competition until he broke his ankle after drinking just days before the competition. He did well in college, felt more accepted, and went on to medical school after getting in from the wait list. He went on to do a pediatrics residency, and he and his wife moved from Indiana to North Carolina so he could do a hematology oncology fellowship. It was toward the end of his 2-year fellowship when he tried to purchase a gun, then walked into those woods.

His wife called, asked him to come to dinner, and he left the woods before he’d overdosed. After a meeting with his wife, parents, and sister, he returned to psychiatric care, restarted antidepressants, went to Alcoholics Anonymous, and told his employer that he had a problem. This admission started a distressing series of events, including years of being monitored by state medical boards and being labeled an “impaired physician.”

This is the only thing I didn’t like about Dr. Hill’s memoir: As open as he is about his emotional life, there were pieces missing with respect to what actually happened. At this point, I was befuddled as to why he self-reported his difficulties, and it wasn’t until he talked about starting a second fellowship in palliative care in his home state of Indiana that I could fill in some missing pieces. Dr. Hill and his wife purchased a house, and in November, he started his fellowship. The timing was off from the usual start in July, and I realized that perhaps he had gone to an inpatient setting for a number of months – his disclosure to his employer was voluntary, but his treatment likely interfered with his training and couldn’t be hidden. What else transpired he hints at: bottles hidden, driving while intoxicated, a nurse who gave him IV hydration when he came to work with a hangover.

From here, Dr. Hill’s story becomes every doctor’s nightmare. Settled into his new house and weeks into his fellowship, he is called in and fired: His application for a medical license in Indiana has been denied because of his addiction history. He met with a friend of his father’s who worked in a large pediatrics practice. The meeting went well, but the group felt he was too much of a malpractice risk.

He now needs to pay his mortgage and student loans, so he takes a position in Oklahoma with the Indian Health Service. He’s 700 miles from home, living alone in a hotel room, feeling like the work is beneath him, and the chapter is titled “Exile.” His new boss greets him with, “Listen, we all had our own stories that led us here.” Surprisingly, he likes the work and feels supported. If only it weren’t for all that loneliness, and not surprisingly, he relapses despite the mandated breathalyzer. Six beers later, and Dr. Hill is off to Chicago for a rehab program, then back to Oklahoma to finish off his stint.

What happens next is the second time I wondered about the plot of his life: Through “connections and concession,” he returns to Indiana for the palliative care fellowship, and goes on to work at Riley Children’s Hospital.

When a colleague unexpectedly dies from suicide, Dr. Hill tells others that he, too, once entertained suicidal thoughts. The story from here gets better and better: He uses his history of addiction and depression to help others – patients, their parents, and other medical professionals – to conquer their shame, to share their stories, to feel less alone. He and his wife become parents, he remains sober and healthy, and therapy leads him to a place of self-discovery and success.

Intertwined with telling his story, Dr. Hill takes on some of the institutional issues surrounding addiction and mental illness. He feels shamed and punished by the state medical board that mandates the terms of his medical license. Any physician who reads this book will think twice about revealing a diagnosis of depression or substance use disorder. It’s not a new idea that to protect the public, medical boards should ask about current impairments, not a past history or conditions that have been successfully treated. They should encourage treatment, not punish those who seek care.

Dr. Hill writes about how helpful it has been to allow himself to be vulnerable in the aftermath:


In my experience, the more vulnerability I show, the more opportunities I have to connect to other people. I learned the hard way that when I hide my true self from others, I spiral toward shame. Conversely, when I bury my shame, I begin to accept myself as a beautifully flawed human being, and my perspective on the world reflects that. A turn of the vulnerability dial has opened up connections to other people, while turning away pity, judgment, fear, and shame. Meanwhile, when I am to create spaces for vulnerability, permission is granted to have open and honest conversations about mental health conditions on a larger scale. But I would never have learned these lessons without having been humbled by this disease.


Perhaps the thing I liked best about Dr. Hill’s memoir is that he proposes some solutions. He talks about the importance of fighting stigma, how he finds it everywhere, and how the medical field equates mental illnesses with weakness, thereby perpetuating a self-deprecating cycle in those who have them.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. Dr. Miller has no disclosures.

Adam B. Hill, MD, is home on a “staycation” this week. Today, he took a 3-hour nap. I know this because I follow Dr. Hill on Twitter, where he has an active feed, a lot of posts, retweets, and more than 20,000 followers.

I also know from Twitter that he is married and has three young children, that he was once suicidal, and has been treated for major depression and alcoholism. As a palliative care doctor, Dr. Hill was required by his state medical board to blow into a breathalyzer several times a day for 5 years – something he felt quite shamed by – and while I’ve never met him, I felt just a little bit proud of this stranger when he was released from the medical board’s oversight.

Dr. Hill’s memoir, “Long Walk Out of the Woods: A Physician’s Story of Addiction, Depression, Hope, and Recovery” (Central Recovery Press, 2019) is the culmination of his efforts to use his difficulties as a way of offering hope and connection to anyone who struggled as he has, or to anyone who has struggled at all. Like his Twitter feed, it is a display of vulnerability and gratitude by someone who has been through dark times then returned to conquer his monsters.

Courtesy Central Recovery Press

He begins by setting the stage for us. “My name is Adam,” he announces in the preface. He tells us his various titles: human being, husband, father, physician, recovering alcoholic, and psychiatric patient. “In the midst of these struggles, working in modern medicine fractured my identity, stole my authenticity, and left me a shell of the person I wanted to be.”

We learn that he tried to buy a gun, but there was a waiting period and he could not purchase the firearm. Instead, he walked into the woods to drink himself to death, with sleeping pills as an add-on – obviously, he didn’t die, and his journey back from his failed suicidal mission is the meat of the book.

Dr. Hill was a quiet and timid child, and he was bullied at school in a way that has lingered on. He struggles with perfectionism and with a sense of never quite belonging. He was a good student, and later a competitive tennis player who was destined for a regional competition until he broke his ankle after drinking just days before the competition. He did well in college, felt more accepted, and went on to medical school after getting in from the wait list. He went on to do a pediatrics residency, and he and his wife moved from Indiana to North Carolina so he could do a hematology oncology fellowship. It was toward the end of his 2-year fellowship when he tried to purchase a gun, then walked into those woods.

His wife called, asked him to come to dinner, and he left the woods before he’d overdosed. After a meeting with his wife, parents, and sister, he returned to psychiatric care, restarted antidepressants, went to Alcoholics Anonymous, and told his employer that he had a problem. This admission started a distressing series of events, including years of being monitored by state medical boards and being labeled an “impaired physician.”

This is the only thing I didn’t like about Dr. Hill’s memoir: As open as he is about his emotional life, there were pieces missing with respect to what actually happened. At this point, I was befuddled as to why he self-reported his difficulties, and it wasn’t until he talked about starting a second fellowship in palliative care in his home state of Indiana that I could fill in some missing pieces. Dr. Hill and his wife purchased a house, and in November, he started his fellowship. The timing was off from the usual start in July, and I realized that perhaps he had gone to an inpatient setting for a number of months – his disclosure to his employer was voluntary, but his treatment likely interfered with his training and couldn’t be hidden. What else transpired he hints at: bottles hidden, driving while intoxicated, a nurse who gave him IV hydration when he came to work with a hangover.

From here, Dr. Hill’s story becomes every doctor’s nightmare. Settled into his new house and weeks into his fellowship, he is called in and fired: His application for a medical license in Indiana has been denied because of his addiction history. He met with a friend of his father’s who worked in a large pediatrics practice. The meeting went well, but the group felt he was too much of a malpractice risk.

He now needs to pay his mortgage and student loans, so he takes a position in Oklahoma with the Indian Health Service. He’s 700 miles from home, living alone in a hotel room, feeling like the work is beneath him, and the chapter is titled “Exile.” His new boss greets him with, “Listen, we all had our own stories that led us here.” Surprisingly, he likes the work and feels supported. If only it weren’t for all that loneliness, and not surprisingly, he relapses despite the mandated breathalyzer. Six beers later, and Dr. Hill is off to Chicago for a rehab program, then back to Oklahoma to finish off his stint.

What happens next is the second time I wondered about the plot of his life: Through “connections and concession,” he returns to Indiana for the palliative care fellowship, and goes on to work at Riley Children’s Hospital.

When a colleague unexpectedly dies from suicide, Dr. Hill tells others that he, too, once entertained suicidal thoughts. The story from here gets better and better: He uses his history of addiction and depression to help others – patients, their parents, and other medical professionals – to conquer their shame, to share their stories, to feel less alone. He and his wife become parents, he remains sober and healthy, and therapy leads him to a place of self-discovery and success.

Intertwined with telling his story, Dr. Hill takes on some of the institutional issues surrounding addiction and mental illness. He feels shamed and punished by the state medical board that mandates the terms of his medical license. Any physician who reads this book will think twice about revealing a diagnosis of depression or substance use disorder. It’s not a new idea that to protect the public, medical boards should ask about current impairments, not a past history or conditions that have been successfully treated. They should encourage treatment, not punish those who seek care.

Dr. Hill writes about how helpful it has been to allow himself to be vulnerable in the aftermath:


In my experience, the more vulnerability I show, the more opportunities I have to connect to other people. I learned the hard way that when I hide my true self from others, I spiral toward shame. Conversely, when I bury my shame, I begin to accept myself as a beautifully flawed human being, and my perspective on the world reflects that. A turn of the vulnerability dial has opened up connections to other people, while turning away pity, judgment, fear, and shame. Meanwhile, when I am to create spaces for vulnerability, permission is granted to have open and honest conversations about mental health conditions on a larger scale. But I would never have learned these lessons without having been humbled by this disease.


Perhaps the thing I liked best about Dr. Hill’s memoir is that he proposes some solutions. He talks about the importance of fighting stigma, how he finds it everywhere, and how the medical field equates mental illnesses with weakness, thereby perpetuating a self-deprecating cycle in those who have them.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. Dr. Miller has no disclosures.

Adam B. Hill, MD, is home on a “staycation” this week. Today, he took a 3-hour nap. I know this because I follow Dr. Hill on Twitter, where he has an active feed, a lot of posts, retweets, and more than 20,000 followers.

I also know from Twitter that he is married and has three young children, that he was once suicidal, and has been treated for major depression and alcoholism. As a palliative care doctor, Dr. Hill was required by his state medical board to blow into a breathalyzer several times a day for 5 years – something he felt quite shamed by – and while I’ve never met him, I felt just a little bit proud of this stranger when he was released from the medical board’s oversight.

Dr. Hill’s memoir, “Long Walk Out of the Woods: A Physician’s Story of Addiction, Depression, Hope, and Recovery” (Central Recovery Press, 2019) is the culmination of his efforts to use his difficulties as a way of offering hope and connection to anyone who struggled as he has, or to anyone who has struggled at all. Like his Twitter feed, it is a display of vulnerability and gratitude by someone who has been through dark times then returned to conquer his monsters.

Courtesy Central Recovery Press

He begins by setting the stage for us. “My name is Adam,” he announces in the preface. He tells us his various titles: human being, husband, father, physician, recovering alcoholic, and psychiatric patient. “In the midst of these struggles, working in modern medicine fractured my identity, stole my authenticity, and left me a shell of the person I wanted to be.”

We learn that he tried to buy a gun, but there was a waiting period and he could not purchase the firearm. Instead, he walked into the woods to drink himself to death, with sleeping pills as an add-on – obviously, he didn’t die, and his journey back from his failed suicidal mission is the meat of the book.

Dr. Hill was a quiet and timid child, and he was bullied at school in a way that has lingered on. He struggles with perfectionism and with a sense of never quite belonging. He was a good student, and later a competitive tennis player who was destined for a regional competition until he broke his ankle after drinking just days before the competition. He did well in college, felt more accepted, and went on to medical school after getting in from the wait list. He went on to do a pediatrics residency, and he and his wife moved from Indiana to North Carolina so he could do a hematology oncology fellowship. It was toward the end of his 2-year fellowship when he tried to purchase a gun, then walked into those woods.

His wife called, asked him to come to dinner, and he left the woods before he’d overdosed. After a meeting with his wife, parents, and sister, he returned to psychiatric care, restarted antidepressants, went to Alcoholics Anonymous, and told his employer that he had a problem. This admission started a distressing series of events, including years of being monitored by state medical boards and being labeled an “impaired physician.”

This is the only thing I didn’t like about Dr. Hill’s memoir: As open as he is about his emotional life, there were pieces missing with respect to what actually happened. At this point, I was befuddled as to why he self-reported his difficulties, and it wasn’t until he talked about starting a second fellowship in palliative care in his home state of Indiana that I could fill in some missing pieces. Dr. Hill and his wife purchased a house, and in November, he started his fellowship. The timing was off from the usual start in July, and I realized that perhaps he had gone to an inpatient setting for a number of months – his disclosure to his employer was voluntary, but his treatment likely interfered with his training and couldn’t be hidden. What else transpired he hints at: bottles hidden, driving while intoxicated, a nurse who gave him IV hydration when he came to work with a hangover.

From here, Dr. Hill’s story becomes every doctor’s nightmare. Settled into his new house and weeks into his fellowship, he is called in and fired: His application for a medical license in Indiana has been denied because of his addiction history. He met with a friend of his father’s who worked in a large pediatrics practice. The meeting went well, but the group felt he was too much of a malpractice risk.

He now needs to pay his mortgage and student loans, so he takes a position in Oklahoma with the Indian Health Service. He’s 700 miles from home, living alone in a hotel room, feeling like the work is beneath him, and the chapter is titled “Exile.” His new boss greets him with, “Listen, we all had our own stories that led us here.” Surprisingly, he likes the work and feels supported. If only it weren’t for all that loneliness, and not surprisingly, he relapses despite the mandated breathalyzer. Six beers later, and Dr. Hill is off to Chicago for a rehab program, then back to Oklahoma to finish off his stint.

What happens next is the second time I wondered about the plot of his life: Through “connections and concession,” he returns to Indiana for the palliative care fellowship, and goes on to work at Riley Children’s Hospital.

When a colleague unexpectedly dies from suicide, Dr. Hill tells others that he, too, once entertained suicidal thoughts. The story from here gets better and better: He uses his history of addiction and depression to help others – patients, their parents, and other medical professionals – to conquer their shame, to share their stories, to feel less alone. He and his wife become parents, he remains sober and healthy, and therapy leads him to a place of self-discovery and success.

Intertwined with telling his story, Dr. Hill takes on some of the institutional issues surrounding addiction and mental illness. He feels shamed and punished by the state medical board that mandates the terms of his medical license. Any physician who reads this book will think twice about revealing a diagnosis of depression or substance use disorder. It’s not a new idea that to protect the public, medical boards should ask about current impairments, not a past history or conditions that have been successfully treated. They should encourage treatment, not punish those who seek care.

Dr. Hill writes about how helpful it has been to allow himself to be vulnerable in the aftermath:


In my experience, the more vulnerability I show, the more opportunities I have to connect to other people. I learned the hard way that when I hide my true self from others, I spiral toward shame. Conversely, when I bury my shame, I begin to accept myself as a beautifully flawed human being, and my perspective on the world reflects that. A turn of the vulnerability dial has opened up connections to other people, while turning away pity, judgment, fear, and shame. Meanwhile, when I am to create spaces for vulnerability, permission is granted to have open and honest conversations about mental health conditions on a larger scale. But I would never have learned these lessons without having been humbled by this disease.


Perhaps the thing I liked best about Dr. Hill’s memoir is that he proposes some solutions. He talks about the importance of fighting stigma, how he finds it everywhere, and how the medical field equates mental illnesses with weakness, thereby perpetuating a self-deprecating cycle in those who have them.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. Dr. Miller has no disclosures.

In heavy drinkers with alcohol-related liver disease, a Markov model based on age, sex, body mass index, and duration and extent of alcohol use predicted risk for disease progression, researchers reported in Clinical Gastroenterology and Hepatology.

The study included 2,334 hospitalized adults with consistently abnormal liver test results who had consumed at least 50 grams of alcohol (about 3.5-4 drinks) per day for the previous 5 years. The model was developed using data from 1,599 individuals with baseline liver biopsies and validated in 735 individuals with no baseline liver biopsies but available data on the presence or absence of hepatic decompensation.

For a 40-year-old man with F0-F2 fibrosis who had been drinking alcohol for 15 years, who drank 150 grams of alcohol daily, and who had a body mass index (BMI) of 22 kg/m², the model predicted a 31.8% likelihood of having a normal liver at baseline, a 61.5% probability of baseline steatosis, and a 6.7% probability of baseline steatohepatitis. In women with the same baseline variables, respective probabilities were 25.1%, 66.5%, and 8.4%. Based on these findings, the 5-year weighted risk for liver complications ranged from 0.2% for men with normal initial liver findings to 10.3% for men with baseline steatohepatitis. Among women, the corresponding risk estimates ranged from 0.5% to 14.7%, wrote PhD student Claire Delacôte of Centre Hospitalier Universitaire de Lille (France), and associates.

“This tool might be used by general practitioners or hepatologists to identify heavy drinkers at high risk for alcohol-related liver disease progression,” the investigators added. “This model might be used to adapt patient care pathways.”

The patients in this study were admitted to the hepatogastroenterology unit of a French hospital between 1982 and 1997. The Markov model incorporated seven stages of alcohol-related liver disease: normal liver (no fibrosis or steatosis), steatosis and F0-F2 fibrosis, alcohol-induced steatohepatitis and F0-F2 fibrosis, steatosis and F3-F4 fibrosis, alcohol-induced steatohepatitis and F3-F4 fibrosis, liver complications without steatohepatitis, and liver complications with alcohol-induced steatohepatitis. Liver complications were defined as hepatocellular carcinoma or liver decompensation (bilirubin >50 mmol/L, gastrointestinal hemorrhage, or ascites). Risk for progressing to liver complications was based on METAVIR score and onset of alcohol-induced steatohepatitis.

The researchers also looked specifically at F3-F4 (severe) fibrosis because of its clinical significance and common use as a study endpoint. Among 40-year-olds with a 15-year history of heavy drinking, the estimated prevalence of alcohol-induced steatohepatitis was 30.0% for men and 33.3% for women. The 5-year risk for liver complications was higher in women (30.1%) than men (24.5%) and was highest among women with baseline alcohol-induced steatohepatitis (41.0%). Overall, women had a 24.8% greater risk for disease progression than men (hazard ratio, 1.248).

Risk for liver complications also increased with age, and each 1-year increase in age at the beginning of heavy drinking heightened the risk for disease progression by 3.8%, regardless of stage of liver disease. “Based on these predictions, 50-year-old women are a high-risk subgroup of [alcohol-related liver] disease progression and should receive close follow-up,” the researchers wrote.

In addition, obese individuals (BMI, 30) had an 11.8% greater risk for progression of alcohol-related liver disease, compared with those with a BMI of 22. Consuming an additional 10 grams of alcohol per day had less impact on risk, the researchers noted.

“If patients are identified as being heavy drinkers by the general practitioner with no evaluation of fibrosis, these patients should be referred to a hepatologist. Nevertheless, we think that the threshold defining the high-risk population, which has been arbitrarily fixed at 5%, should be discussed by experts because it affects the patient’s care pathway. An online application is being developed to help clinicians and general practitioners in their daily practice,” they wrote.

No funding sources were reported. Ms. Delacôte reported having no conflicts of interest. Three coinvestigators disclosed ties to AbbVie, Bayer Healthcare, Eisai, Gilead, MSD, Novartis, Sanofi, and Servier. The others reported having no conflicts.
 

SOURCE: Delacôte C et al. Clin Gastroenterol Hepatol. 2020 Jan 11. doi: 10.1016/j.cgh.2019.12.041.
 

In heavy drinkers with alcohol-related liver disease, a Markov model based on age, sex, body mass index, and duration and extent of alcohol use predicted risk for disease progression, researchers reported in Clinical Gastroenterology and Hepatology.

The study included 2,334 hospitalized adults with consistently abnormal liver test results who had consumed at least 50 grams of alcohol (about 3.5-4 drinks) per day for the previous 5 years. The model was developed using data from 1,599 individuals with baseline liver biopsies and validated in 735 individuals with no baseline liver biopsies but available data on the presence or absence of hepatic decompensation.

For a 40-year-old man with F0-F2 fibrosis who had been drinking alcohol for 15 years, who drank 150 grams of alcohol daily, and who had a body mass index (BMI) of 22 kg/m², the model predicted a 31.8% likelihood of having a normal liver at baseline, a 61.5% probability of baseline steatosis, and a 6.7% probability of baseline steatohepatitis. In women with the same baseline variables, respective probabilities were 25.1%, 66.5%, and 8.4%. Based on these findings, the 5-year weighted risk for liver complications ranged from 0.2% for men with normal initial liver findings to 10.3% for men with baseline steatohepatitis. Among women, the corresponding risk estimates ranged from 0.5% to 14.7%, wrote PhD student Claire Delacôte of Centre Hospitalier Universitaire de Lille (France), and associates.

“This tool might be used by general practitioners or hepatologists to identify heavy drinkers at high risk for alcohol-related liver disease progression,” the investigators added. “This model might be used to adapt patient care pathways.”

The patients in this study were admitted to the hepatogastroenterology unit of a French hospital between 1982 and 1997. The Markov model incorporated seven stages of alcohol-related liver disease: normal liver (no fibrosis or steatosis), steatosis and F0-F2 fibrosis, alcohol-induced steatohepatitis and F0-F2 fibrosis, steatosis and F3-F4 fibrosis, alcohol-induced steatohepatitis and F3-F4 fibrosis, liver complications without steatohepatitis, and liver complications with alcohol-induced steatohepatitis. Liver complications were defined as hepatocellular carcinoma or liver decompensation (bilirubin >50 mmol/L, gastrointestinal hemorrhage, or ascites). Risk for progressing to liver complications was based on METAVIR score and onset of alcohol-induced steatohepatitis.

The researchers also looked specifically at F3-F4 (severe) fibrosis because of its clinical significance and common use as a study endpoint. Among 40-year-olds with a 15-year history of heavy drinking, the estimated prevalence of alcohol-induced steatohepatitis was 30.0% for men and 33.3% for women. The 5-year risk for liver complications was higher in women (30.1%) than men (24.5%) and was highest among women with baseline alcohol-induced steatohepatitis (41.0%). Overall, women had a 24.8% greater risk for disease progression than men (hazard ratio, 1.248).

Risk for liver complications also increased with age, and each 1-year increase in age at the beginning of heavy drinking heightened the risk for disease progression by 3.8%, regardless of stage of liver disease. “Based on these predictions, 50-year-old women are a high-risk subgroup of [alcohol-related liver] disease progression and should receive close follow-up,” the researchers wrote.

In addition, obese individuals (BMI, 30) had an 11.8% greater risk for progression of alcohol-related liver disease, compared with those with a BMI of 22. Consuming an additional 10 grams of alcohol per day had less impact on risk, the researchers noted.

“If patients are identified as being heavy drinkers by the general practitioner with no evaluation of fibrosis, these patients should be referred to a hepatologist. Nevertheless, we think that the threshold defining the high-risk population, which has been arbitrarily fixed at 5%, should be discussed by experts because it affects the patient’s care pathway. An online application is being developed to help clinicians and general practitioners in their daily practice,” they wrote.

No funding sources were reported. Ms. Delacôte reported having no conflicts of interest. Three coinvestigators disclosed ties to AbbVie, Bayer Healthcare, Eisai, Gilead, MSD, Novartis, Sanofi, and Servier. The others reported having no conflicts.
 

SOURCE: Delacôte C et al. Clin Gastroenterol Hepatol. 2020 Jan 11. doi: 10.1016/j.cgh.2019.12.041.
 

In heavy drinkers with alcohol-related liver disease, a Markov model based on age, sex, body mass index, and duration and extent of alcohol use predicted risk for disease progression, researchers reported in Clinical Gastroenterology and Hepatology.

The study included 2,334 hospitalized adults with consistently abnormal liver test results who had consumed at least 50 grams of alcohol (about 3.5-4 drinks) per day for the previous 5 years. The model was developed using data from 1,599 individuals with baseline liver biopsies and validated in 735 individuals with no baseline liver biopsies but available data on the presence or absence of hepatic decompensation.

For a 40-year-old man with F0-F2 fibrosis who had been drinking alcohol for 15 years, who drank 150 grams of alcohol daily, and who had a body mass index (BMI) of 22 kg/m², the model predicted a 31.8% likelihood of having a normal liver at baseline, a 61.5% probability of baseline steatosis, and a 6.7% probability of baseline steatohepatitis. In women with the same baseline variables, respective probabilities were 25.1%, 66.5%, and 8.4%. Based on these findings, the 5-year weighted risk for liver complications ranged from 0.2% for men with normal initial liver findings to 10.3% for men with baseline steatohepatitis. Among women, the corresponding risk estimates ranged from 0.5% to 14.7%, wrote PhD student Claire Delacôte of Centre Hospitalier Universitaire de Lille (France), and associates.

“This tool might be used by general practitioners or hepatologists to identify heavy drinkers at high risk for alcohol-related liver disease progression,” the investigators added. “This model might be used to adapt patient care pathways.”

The patients in this study were admitted to the hepatogastroenterology unit of a French hospital between 1982 and 1997. The Markov model incorporated seven stages of alcohol-related liver disease: normal liver (no fibrosis or steatosis), steatosis and F0-F2 fibrosis, alcohol-induced steatohepatitis and F0-F2 fibrosis, steatosis and F3-F4 fibrosis, alcohol-induced steatohepatitis and F3-F4 fibrosis, liver complications without steatohepatitis, and liver complications with alcohol-induced steatohepatitis. Liver complications were defined as hepatocellular carcinoma or liver decompensation (bilirubin >50 mmol/L, gastrointestinal hemorrhage, or ascites). Risk for progressing to liver complications was based on METAVIR score and onset of alcohol-induced steatohepatitis.

The researchers also looked specifically at F3-F4 (severe) fibrosis because of its clinical significance and common use as a study endpoint. Among 40-year-olds with a 15-year history of heavy drinking, the estimated prevalence of alcohol-induced steatohepatitis was 30.0% for men and 33.3% for women. The 5-year risk for liver complications was higher in women (30.1%) than men (24.5%) and was highest among women with baseline alcohol-induced steatohepatitis (41.0%). Overall, women had a 24.8% greater risk for disease progression than men (hazard ratio, 1.248).

Risk for liver complications also increased with age, and each 1-year increase in age at the beginning of heavy drinking heightened the risk for disease progression by 3.8%, regardless of stage of liver disease. “Based on these predictions, 50-year-old women are a high-risk subgroup of [alcohol-related liver] disease progression and should receive close follow-up,” the researchers wrote.

In addition, obese individuals (BMI, 30) had an 11.8% greater risk for progression of alcohol-related liver disease, compared with those with a BMI of 22. Consuming an additional 10 grams of alcohol per day had less impact on risk, the researchers noted.

“If patients are identified as being heavy drinkers by the general practitioner with no evaluation of fibrosis, these patients should be referred to a hepatologist. Nevertheless, we think that the threshold defining the high-risk population, which has been arbitrarily fixed at 5%, should be discussed by experts because it affects the patient’s care pathway. An online application is being developed to help clinicians and general practitioners in their daily practice,” they wrote.

No funding sources were reported. Ms. Delacôte reported having no conflicts of interest. Three coinvestigators disclosed ties to AbbVie, Bayer Healthcare, Eisai, Gilead, MSD, Novartis, Sanofi, and Servier. The others reported having no conflicts.
 

SOURCE: Delacôte C et al. Clin Gastroenterol Hepatol. 2020 Jan 11. doi: 10.1016/j.cgh.2019.12.041.
 

Among adults who consumed a proinflammatory diet, switching to a diet with lower inflammatory potential was associated with a significant subsequent decrease in risk for Crohn’s disease, according to a study of three longitudinal observational cohorts.

Researchers calculated empirical dietary inflammatory pattern (EDIP) scores based on food-frequency questionnaires completed by 166,903 women and 41,931 men who participated in the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. Questionnaires were completed at two time points, separated by 8 years. Overall, adults whose cumulative average EDIP scores fell within the highest quartile – meaning their diets had the highest inflammatory potential – were at 51% greater risk for developing Crohn’s disease than were adults whose diets fell within the lowest EDIP quartile (hazard ratio, 1.51; 95% confidence interval, 1.19-2.07; P = .01).

Strikingly, however, adults who initially consumed a proinflammatory diet (which is high in calories, red meat, high-fat dairy, and refined grains) and then switched to a low-inflammatory diet (one based around fruit, vegetables, legumes, whole grains, fish, and lean protein) had a statistically similar risk for Crohn’s disease as adults who consumed a low-inflammatory diet at both time points. The 95% confidence interval for the hazard ratio crossed 1.0 (HR, 1.51; 95% CI, 0.76-3.00). In contrast, adults who initially consumed a low-inflammatory diet and later changed to a proinflammatory diet were at twofold greater risk for Crohn’s disease than were those who remained on a low-inflammatory diet (HR, 2.05; 95% CI, 1.10-3.79).

These findings accounted for potential confounders, such as age, study cohort, time period, race, smoking, physical activity, and use of oral contraceptives and hormone replacement therapy, wrote Chun-Han Lo, MD, of the Harvard T.H. Chan School of Public Health, Boston, together with his associates in Gastroenterology.

The EDIP score is a weighted sum of 18 food groups that characterizes the potential for dietary inflammation based on circulating concentrations of inflammatory biomarkers. A proinflammatory diet may “trigger the onset of intestinal inflammation by inducing changes in [the] gut microbiome, altering host homeostasis, and regulating T-cell immune response,” the investigators noted.

In this study, which included nearly 5 million person-years of follow-up, 328 individuals were diagnosed with Crohn’s disease and 428 individuals developed ulcerative colitis. Median age at inflammatory bowel disease diagnosis was 55 years, with a range of 29-85 years. Notably, change in EDIP score was not linked to ulcerative colitis risk. Diet may be more relevant in Crohn’s disease than ulcerative colitis, and dietary factors linked to ulcerative colitis were not associated with inflammatory markers in the cohorts and, thus, were not factored into EDIP score, the researchers wrote.

The link between EDIP score and Crohn’s disease in this study did not change after controlling for fiber intake. Red wine (which contains anti-inflammatory resveratrol) might be a protective factor, the researchers hypothesized. They also found that pizza – a processed, calorie-dense food – was significantly inversely linked to inflammatory markers, perhaps because pizza contains abundant lycopene (from tomato paste) and fat (which facilitate lycopene absorption).

Prior studies on diet and inflammatory bowel disease assessed diets at only one time point and categorized dietary habits based on food groups, rather than linking foods with inflammatory markers, the researchers wrote. “Here, by identifying a combination of food groups predictive of circulating markers of inflammation, we provide a more robust evidence base behind the association of these foods with inflammation and inflammatory bowel disease.”

Most study participants were white health professionals. The researchers noted that “studies of dietary risk factors have not revealed a strong ethnicity-specific association, [but] extrapolating our findings to individuals of other ethnicity should be performed with caution.”

The National Institutes of Health, the Beker Foundation, the Chleck Family Foundation, and the Crohn’s and Colitis Foundation provided funding. Three coinvestigators disclosed ties to AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Gilead, Janssen, Kyn Therapeutics, Merck Pfizer, Policy Analysis Inc., and Takeda.

SOURCE: Lo C-H et al. Gastroenterology. 2020 May 1. doi: 10.1053/j.gastro.2020.05.011.
 

Among adults who consumed a proinflammatory diet, switching to a diet with lower inflammatory potential was associated with a significant subsequent decrease in risk for Crohn’s disease, according to a study of three longitudinal observational cohorts.

Researchers calculated empirical dietary inflammatory pattern (EDIP) scores based on food-frequency questionnaires completed by 166,903 women and 41,931 men who participated in the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. Questionnaires were completed at two time points, separated by 8 years. Overall, adults whose cumulative average EDIP scores fell within the highest quartile – meaning their diets had the highest inflammatory potential – were at 51% greater risk for developing Crohn’s disease than were adults whose diets fell within the lowest EDIP quartile (hazard ratio, 1.51; 95% confidence interval, 1.19-2.07; P = .01).

Strikingly, however, adults who initially consumed a proinflammatory diet (which is high in calories, red meat, high-fat dairy, and refined grains) and then switched to a low-inflammatory diet (one based around fruit, vegetables, legumes, whole grains, fish, and lean protein) had a statistically similar risk for Crohn’s disease as adults who consumed a low-inflammatory diet at both time points. The 95% confidence interval for the hazard ratio crossed 1.0 (HR, 1.51; 95% CI, 0.76-3.00). In contrast, adults who initially consumed a low-inflammatory diet and later changed to a proinflammatory diet were at twofold greater risk for Crohn’s disease than were those who remained on a low-inflammatory diet (HR, 2.05; 95% CI, 1.10-3.79).

These findings accounted for potential confounders, such as age, study cohort, time period, race, smoking, physical activity, and use of oral contraceptives and hormone replacement therapy, wrote Chun-Han Lo, MD, of the Harvard T.H. Chan School of Public Health, Boston, together with his associates in Gastroenterology.

The EDIP score is a weighted sum of 18 food groups that characterizes the potential for dietary inflammation based on circulating concentrations of inflammatory biomarkers. A proinflammatory diet may “trigger the onset of intestinal inflammation by inducing changes in [the] gut microbiome, altering host homeostasis, and regulating T-cell immune response,” the investigators noted.

In this study, which included nearly 5 million person-years of follow-up, 328 individuals were diagnosed with Crohn’s disease and 428 individuals developed ulcerative colitis. Median age at inflammatory bowel disease diagnosis was 55 years, with a range of 29-85 years. Notably, change in EDIP score was not linked to ulcerative colitis risk. Diet may be more relevant in Crohn’s disease than ulcerative colitis, and dietary factors linked to ulcerative colitis were not associated with inflammatory markers in the cohorts and, thus, were not factored into EDIP score, the researchers wrote.

The link between EDIP score and Crohn’s disease in this study did not change after controlling for fiber intake. Red wine (which contains anti-inflammatory resveratrol) might be a protective factor, the researchers hypothesized. They also found that pizza – a processed, calorie-dense food – was significantly inversely linked to inflammatory markers, perhaps because pizza contains abundant lycopene (from tomato paste) and fat (which facilitate lycopene absorption).

Prior studies on diet and inflammatory bowel disease assessed diets at only one time point and categorized dietary habits based on food groups, rather than linking foods with inflammatory markers, the researchers wrote. “Here, by identifying a combination of food groups predictive of circulating markers of inflammation, we provide a more robust evidence base behind the association of these foods with inflammation and inflammatory bowel disease.”

Most study participants were white health professionals. The researchers noted that “studies of dietary risk factors have not revealed a strong ethnicity-specific association, [but] extrapolating our findings to individuals of other ethnicity should be performed with caution.”

The National Institutes of Health, the Beker Foundation, the Chleck Family Foundation, and the Crohn’s and Colitis Foundation provided funding. Three coinvestigators disclosed ties to AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Gilead, Janssen, Kyn Therapeutics, Merck Pfizer, Policy Analysis Inc., and Takeda.

SOURCE: Lo C-H et al. Gastroenterology. 2020 May 1. doi: 10.1053/j.gastro.2020.05.011.
 

Among adults who consumed a proinflammatory diet, switching to a diet with lower inflammatory potential was associated with a significant subsequent decrease in risk for Crohn’s disease, according to a study of three longitudinal observational cohorts.

Researchers calculated empirical dietary inflammatory pattern (EDIP) scores based on food-frequency questionnaires completed by 166,903 women and 41,931 men who participated in the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. Questionnaires were completed at two time points, separated by 8 years. Overall, adults whose cumulative average EDIP scores fell within the highest quartile – meaning their diets had the highest inflammatory potential – were at 51% greater risk for developing Crohn’s disease than were adults whose diets fell within the lowest EDIP quartile (hazard ratio, 1.51; 95% confidence interval, 1.19-2.07; P = .01).

Strikingly, however, adults who initially consumed a proinflammatory diet (which is high in calories, red meat, high-fat dairy, and refined grains) and then switched to a low-inflammatory diet (one based around fruit, vegetables, legumes, whole grains, fish, and lean protein) had a statistically similar risk for Crohn’s disease as adults who consumed a low-inflammatory diet at both time points. The 95% confidence interval for the hazard ratio crossed 1.0 (HR, 1.51; 95% CI, 0.76-3.00). In contrast, adults who initially consumed a low-inflammatory diet and later changed to a proinflammatory diet were at twofold greater risk for Crohn’s disease than were those who remained on a low-inflammatory diet (HR, 2.05; 95% CI, 1.10-3.79).

These findings accounted for potential confounders, such as age, study cohort, time period, race, smoking, physical activity, and use of oral contraceptives and hormone replacement therapy, wrote Chun-Han Lo, MD, of the Harvard T.H. Chan School of Public Health, Boston, together with his associates in Gastroenterology.

The EDIP score is a weighted sum of 18 food groups that characterizes the potential for dietary inflammation based on circulating concentrations of inflammatory biomarkers. A proinflammatory diet may “trigger the onset of intestinal inflammation by inducing changes in [the] gut microbiome, altering host homeostasis, and regulating T-cell immune response,” the investigators noted.

In this study, which included nearly 5 million person-years of follow-up, 328 individuals were diagnosed with Crohn’s disease and 428 individuals developed ulcerative colitis. Median age at inflammatory bowel disease diagnosis was 55 years, with a range of 29-85 years. Notably, change in EDIP score was not linked to ulcerative colitis risk. Diet may be more relevant in Crohn’s disease than ulcerative colitis, and dietary factors linked to ulcerative colitis were not associated with inflammatory markers in the cohorts and, thus, were not factored into EDIP score, the researchers wrote.

The link between EDIP score and Crohn’s disease in this study did not change after controlling for fiber intake. Red wine (which contains anti-inflammatory resveratrol) might be a protective factor, the researchers hypothesized. They also found that pizza – a processed, calorie-dense food – was significantly inversely linked to inflammatory markers, perhaps because pizza contains abundant lycopene (from tomato paste) and fat (which facilitate lycopene absorption).

Prior studies on diet and inflammatory bowel disease assessed diets at only one time point and categorized dietary habits based on food groups, rather than linking foods with inflammatory markers, the researchers wrote. “Here, by identifying a combination of food groups predictive of circulating markers of inflammation, we provide a more robust evidence base behind the association of these foods with inflammation and inflammatory bowel disease.”

Most study participants were white health professionals. The researchers noted that “studies of dietary risk factors have not revealed a strong ethnicity-specific association, [but] extrapolating our findings to individuals of other ethnicity should be performed with caution.”

The National Institutes of Health, the Beker Foundation, the Chleck Family Foundation, and the Crohn’s and Colitis Foundation provided funding. Three coinvestigators disclosed ties to AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Gilead, Janssen, Kyn Therapeutics, Merck Pfizer, Policy Analysis Inc., and Takeda.

SOURCE: Lo C-H et al. Gastroenterology. 2020 May 1. doi: 10.1053/j.gastro.2020.05.011.