NASHVILLE – Advising patients in a comprehensive weight loss intervention to moderate their alcohol consumption did not change how much they drank over the long term. At the same time, abstinent patients kept off more weight over time than those who were classified as heavy drinkers, in a new analysis of data from a multicenter trial.

Kari Oakes/MDedge News

Abstinent individuals lost just 1.6% more of their body weight after 4 years than those who drank (P = .003), a figure with “uncertain clinical significance,” Ariana Chao, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. “The results should be taken in the context of the potential – though controversial – benefits of light to moderate alcohol consumption,” she added.

Alcohol contains 7.1 kcal/g, and “calories from alcohol usually add, rather than substitute, for food intake,” said Dr. Chao. Alcohol’s disinhibiting effects are thought to contribute to increased food intake and the making of less healthy food choices. However, existing research has shown inconsistent findings about the relationship between alcohol consumption and body weight, she said.

Reducing or completely cutting out alcoholic beverage consumption is common advice for those trying to lose weight, but whether this advice is followed, and whether it makes a difference over the long term, has been an open question, said Dr. Chao.

She and her collaborators at the University of Pennsylvania, Philadelphia, used data from Look AHEAD, “a multicenter, randomized, clinical trial that compared an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group,” for 5,145 people with overweight or obesity and type 2 diabetes, explained Dr. Chao and her coinvestigators.

Dr. Chao and her colleagues looked at the effect that the lifestyle intervention had on alcohol consumption. Additionally, to see how drinkers and nondrinkers fared over the long term, they examined the interaction between alcohol consumption and weight loss at year 4, hypothesizing that individuals who received ILI would have a greater decrease in their alcohol consumption by year 4 than those who received DSE. The investigators had a second hypothesis that, among the ILI cohort, greater alcohol consumption would be associated with less weight loss over the 4 years studied.

To measure alcohol consumption, participants completed a questionnaire at baseline and annually thereafter. The questionnaire asked whether participants had consumed any alcoholic beverages in the past week, and how many drinks per week of wine, beer, or liquor per week were typical for those who did consume alcohol.

Respondents were grouped into four categories according to their baseline alcohol consumption: nondrinkers, light drinkers (fewer than 7 drinks weekly for men and 4 for women), moderate drinkers (7-14 drinks weekly for men and 4-7 for women), and heavy drinkers (more than 14 drinks weekly for men and 7 for women).

At baseline, 38% of participants reported being abstinent from alcohol, and about 54% reported being light drinkers. Moderate drinkers made up 6%, and 2% reported falling into the heavy drinking category. Females were more likely than males to be nondrinkers.

Heavy drinkers took in significantly more calories than nondrinkers at baseline (2,397 versus 1,907 kcal/day; P less than .001).

Individuals who had consistently been heavy drinkers throughout the study lost less weight than any other group, dropping just 2.4% of their body weight at year 4, compared with their baseline weight. Those who were abstinent from alcohol fared the best, losing 5.1% of their initial body weight (P = .04 for difference). “Heavy drinking is a risk factor for suboptimal long-term weight loss,” said Dr. Chao.

Even those who were consistent light drinkers lost a bit less than those who were abstinent, keeping off 4.2% of their baseline body weight at 4 years (P = .04).

Look AHEAD included individuals aged 45-76 years with type 2 diabetes mellitus and a body mass index of at least 25 kg/m², or 27 kg/m² for those on insulin. Excluded were those with hemoglobin A_1c of at least 11%, blood pressure of at least 160/100 mm Hg, and triglycerides over 600 mg/dL. A total of 4,901 patients had complete data available in the public access data set and were included in the present analysis. Dr. Chao and her colleagues used statistical techniques to adjust for baseline differences among participants.

The three-part ILI in Look AHEAD began by encouraging a low-calorie diet of 1,200-1,500 kcal/day for those weighing under 250 pounds, and 1,500-1,800 kcal/day for those who were heavier at baseline. Advice was to consume a balanced diet with less than 30% fat, less than 10% saturated fat, and at least 15% protein.

Patients were advised to strive for 10,000 steps per day, with 175 minutes of moderate-intensity exercise each week. Exercise was unsupervised.

Behavioral modification techniques included goal-setting, stimulus control, self-monitoring, and ideas for problem solving and relapse prevention. The intervention used motivational interviewing techniques.

With regard to alcohol, the ILI group was given information about the number of calories in various alcoholic beverages and advised to reduce the amount of alcohol consumed, in order to reduce calories.

The DSE group participated in three group sessions annually, and received general information about nutrition, exercise, and general support.

A potentially important limitation of the study was that alcohol consumption was assessed by self-report and a request for annual recall of typical drinking habits. An audience member from the United Kingdom commented that she found the overall rate of reported alcohol consumption to be “shockingly low,” compared with what her patients report drinking in England. The average United States resident drinks 2.3 gallons of alcohol, or 494 standard drinks, annually, according to the National Institute on Alcohol Abuse and Alcoholism, said Dr. Chao.

The midlife age range of participants, their diabetes diagnosis, and the fact that depressive symptoms were overall low limits generalizability of the findings, said Dr. Chao, adding that psychosocial factors, other health conditions, and current or past alcohol use disorder could also cause some residual confounding of the data.

Dr. Chao has received research support from Shire Pharmaceuticals.

[email protected]

SOURCE: Chao A et al. Obesity Week 2018, Abstract T-OR-2017.

NASHVILLE – Advising patients in a comprehensive weight loss intervention to moderate their alcohol consumption did not change how much they drank over the long term. At the same time, abstinent patients kept off more weight over time than those who were classified as heavy drinkers, in a new analysis of data from a multicenter trial.

Kari Oakes/MDedge News

Abstinent individuals lost just 1.6% more of their body weight after 4 years than those who drank (P = .003), a figure with “uncertain clinical significance,” Ariana Chao, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. “The results should be taken in the context of the potential – though controversial – benefits of light to moderate alcohol consumption,” she added.

Alcohol contains 7.1 kcal/g, and “calories from alcohol usually add, rather than substitute, for food intake,” said Dr. Chao. Alcohol’s disinhibiting effects are thought to contribute to increased food intake and the making of less healthy food choices. However, existing research has shown inconsistent findings about the relationship between alcohol consumption and body weight, she said.

Reducing or completely cutting out alcoholic beverage consumption is common advice for those trying to lose weight, but whether this advice is followed, and whether it makes a difference over the long term, has been an open question, said Dr. Chao.

She and her collaborators at the University of Pennsylvania, Philadelphia, used data from Look AHEAD, “a multicenter, randomized, clinical trial that compared an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group,” for 5,145 people with overweight or obesity and type 2 diabetes, explained Dr. Chao and her coinvestigators.

Dr. Chao and her colleagues looked at the effect that the lifestyle intervention had on alcohol consumption. Additionally, to see how drinkers and nondrinkers fared over the long term, they examined the interaction between alcohol consumption and weight loss at year 4, hypothesizing that individuals who received ILI would have a greater decrease in their alcohol consumption by year 4 than those who received DSE. The investigators had a second hypothesis that, among the ILI cohort, greater alcohol consumption would be associated with less weight loss over the 4 years studied.

To measure alcohol consumption, participants completed a questionnaire at baseline and annually thereafter. The questionnaire asked whether participants had consumed any alcoholic beverages in the past week, and how many drinks per week of wine, beer, or liquor per week were typical for those who did consume alcohol.

Respondents were grouped into four categories according to their baseline alcohol consumption: nondrinkers, light drinkers (fewer than 7 drinks weekly for men and 4 for women), moderate drinkers (7-14 drinks weekly for men and 4-7 for women), and heavy drinkers (more than 14 drinks weekly for men and 7 for women).

At baseline, 38% of participants reported being abstinent from alcohol, and about 54% reported being light drinkers. Moderate drinkers made up 6%, and 2% reported falling into the heavy drinking category. Females were more likely than males to be nondrinkers.

Heavy drinkers took in significantly more calories than nondrinkers at baseline (2,397 versus 1,907 kcal/day; P less than .001).

Individuals who had consistently been heavy drinkers throughout the study lost less weight than any other group, dropping just 2.4% of their body weight at year 4, compared with their baseline weight. Those who were abstinent from alcohol fared the best, losing 5.1% of their initial body weight (P = .04 for difference). “Heavy drinking is a risk factor for suboptimal long-term weight loss,” said Dr. Chao.

Even those who were consistent light drinkers lost a bit less than those who were abstinent, keeping off 4.2% of their baseline body weight at 4 years (P = .04).

Look AHEAD included individuals aged 45-76 years with type 2 diabetes mellitus and a body mass index of at least 25 kg/m², or 27 kg/m² for those on insulin. Excluded were those with hemoglobin A_1c of at least 11%, blood pressure of at least 160/100 mm Hg, and triglycerides over 600 mg/dL. A total of 4,901 patients had complete data available in the public access data set and were included in the present analysis. Dr. Chao and her colleagues used statistical techniques to adjust for baseline differences among participants.

The three-part ILI in Look AHEAD began by encouraging a low-calorie diet of 1,200-1,500 kcal/day for those weighing under 250 pounds, and 1,500-1,800 kcal/day for those who were heavier at baseline. Advice was to consume a balanced diet with less than 30% fat, less than 10% saturated fat, and at least 15% protein.

Patients were advised to strive for 10,000 steps per day, with 175 minutes of moderate-intensity exercise each week. Exercise was unsupervised.

Behavioral modification techniques included goal-setting, stimulus control, self-monitoring, and ideas for problem solving and relapse prevention. The intervention used motivational interviewing techniques.

With regard to alcohol, the ILI group was given information about the number of calories in various alcoholic beverages and advised to reduce the amount of alcohol consumed, in order to reduce calories.

The DSE group participated in three group sessions annually, and received general information about nutrition, exercise, and general support.

A potentially important limitation of the study was that alcohol consumption was assessed by self-report and a request for annual recall of typical drinking habits. An audience member from the United Kingdom commented that she found the overall rate of reported alcohol consumption to be “shockingly low,” compared with what her patients report drinking in England. The average United States resident drinks 2.3 gallons of alcohol, or 494 standard drinks, annually, according to the National Institute on Alcohol Abuse and Alcoholism, said Dr. Chao.

The midlife age range of participants, their diabetes diagnosis, and the fact that depressive symptoms were overall low limits generalizability of the findings, said Dr. Chao, adding that psychosocial factors, other health conditions, and current or past alcohol use disorder could also cause some residual confounding of the data.

Dr. Chao has received research support from Shire Pharmaceuticals.

[email protected]

SOURCE: Chao A et al. Obesity Week 2018, Abstract T-OR-2017.

NASHVILLE – Advising patients in a comprehensive weight loss intervention to moderate their alcohol consumption did not change how much they drank over the long term. At the same time, abstinent patients kept off more weight over time than those who were classified as heavy drinkers, in a new analysis of data from a multicenter trial.

Kari Oakes/MDedge News

Abstinent individuals lost just 1.6% more of their body weight after 4 years than those who drank (P = .003), a figure with “uncertain clinical significance,” Ariana Chao, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. “The results should be taken in the context of the potential – though controversial – benefits of light to moderate alcohol consumption,” she added.

Alcohol contains 7.1 kcal/g, and “calories from alcohol usually add, rather than substitute, for food intake,” said Dr. Chao. Alcohol’s disinhibiting effects are thought to contribute to increased food intake and the making of less healthy food choices. However, existing research has shown inconsistent findings about the relationship between alcohol consumption and body weight, she said.

Reducing or completely cutting out alcoholic beverage consumption is common advice for those trying to lose weight, but whether this advice is followed, and whether it makes a difference over the long term, has been an open question, said Dr. Chao.

She and her collaborators at the University of Pennsylvania, Philadelphia, used data from Look AHEAD, “a multicenter, randomized, clinical trial that compared an intensive lifestyle intervention (ILI) to a diabetes support and education (DSE) control group,” for 5,145 people with overweight or obesity and type 2 diabetes, explained Dr. Chao and her coinvestigators.

Dr. Chao and her colleagues looked at the effect that the lifestyle intervention had on alcohol consumption. Additionally, to see how drinkers and nondrinkers fared over the long term, they examined the interaction between alcohol consumption and weight loss at year 4, hypothesizing that individuals who received ILI would have a greater decrease in their alcohol consumption by year 4 than those who received DSE. The investigators had a second hypothesis that, among the ILI cohort, greater alcohol consumption would be associated with less weight loss over the 4 years studied.

To measure alcohol consumption, participants completed a questionnaire at baseline and annually thereafter. The questionnaire asked whether participants had consumed any alcoholic beverages in the past week, and how many drinks per week of wine, beer, or liquor per week were typical for those who did consume alcohol.

Respondents were grouped into four categories according to their baseline alcohol consumption: nondrinkers, light drinkers (fewer than 7 drinks weekly for men and 4 for women), moderate drinkers (7-14 drinks weekly for men and 4-7 for women), and heavy drinkers (more than 14 drinks weekly for men and 7 for women).

At baseline, 38% of participants reported being abstinent from alcohol, and about 54% reported being light drinkers. Moderate drinkers made up 6%, and 2% reported falling into the heavy drinking category. Females were more likely than males to be nondrinkers.

Heavy drinkers took in significantly more calories than nondrinkers at baseline (2,397 versus 1,907 kcal/day; P less than .001).

Individuals who had consistently been heavy drinkers throughout the study lost less weight than any other group, dropping just 2.4% of their body weight at year 4, compared with their baseline weight. Those who were abstinent from alcohol fared the best, losing 5.1% of their initial body weight (P = .04 for difference). “Heavy drinking is a risk factor for suboptimal long-term weight loss,” said Dr. Chao.

Even those who were consistent light drinkers lost a bit less than those who were abstinent, keeping off 4.2% of their baseline body weight at 4 years (P = .04).

Look AHEAD included individuals aged 45-76 years with type 2 diabetes mellitus and a body mass index of at least 25 kg/m², or 27 kg/m² for those on insulin. Excluded were those with hemoglobin A_1c of at least 11%, blood pressure of at least 160/100 mm Hg, and triglycerides over 600 mg/dL. A total of 4,901 patients had complete data available in the public access data set and were included in the present analysis. Dr. Chao and her colleagues used statistical techniques to adjust for baseline differences among participants.

The three-part ILI in Look AHEAD began by encouraging a low-calorie diet of 1,200-1,500 kcal/day for those weighing under 250 pounds, and 1,500-1,800 kcal/day for those who were heavier at baseline. Advice was to consume a balanced diet with less than 30% fat, less than 10% saturated fat, and at least 15% protein.

Patients were advised to strive for 10,000 steps per day, with 175 minutes of moderate-intensity exercise each week. Exercise was unsupervised.

Behavioral modification techniques included goal-setting, stimulus control, self-monitoring, and ideas for problem solving and relapse prevention. The intervention used motivational interviewing techniques.

With regard to alcohol, the ILI group was given information about the number of calories in various alcoholic beverages and advised to reduce the amount of alcohol consumed, in order to reduce calories.

The DSE group participated in three group sessions annually, and received general information about nutrition, exercise, and general support.

A potentially important limitation of the study was that alcohol consumption was assessed by self-report and a request for annual recall of typical drinking habits. An audience member from the United Kingdom commented that she found the overall rate of reported alcohol consumption to be “shockingly low,” compared with what her patients report drinking in England. The average United States resident drinks 2.3 gallons of alcohol, or 494 standard drinks, annually, according to the National Institute on Alcohol Abuse and Alcoholism, said Dr. Chao.

The midlife age range of participants, their diabetes diagnosis, and the fact that depressive symptoms were overall low limits generalizability of the findings, said Dr. Chao, adding that psychosocial factors, other health conditions, and current or past alcohol use disorder could also cause some residual confounding of the data.

Dr. Chao has received research support from Shire Pharmaceuticals.

[email protected]

SOURCE: Chao A et al. Obesity Week 2018, Abstract T-OR-2017.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

[email protected]

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

[email protected]

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

[email protected]

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

PARIS – A major worldwide survey of the 12-month prevalence of atopic dermatitis (AD) across the course of life provides new insights into global disease trends, Jonathan I. Silverberg, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Among the most important takeaways from this Internet-based survey of more than 273,645 infants, children, and adults in 18 countries across five continents conducted in 2017 was that “global atopic dermatitis prevalence appears to be higher in adults, at 10%, than in younger cohorts, where it’s 4%-8%, which I think is quite provocative and requires further study and confirmation,” said Dr. Silverberg, a dermatologist at Northwestern University in Chicago.

“Let’s keep in mind that there’s this accepted dogma in the literature than atopic dermatitis is somehow only a childhood disorder – it doesn’t affect adults. Well, these data tell a very different story because we’re actually seeing overall highest prevalences throughout the world occurring in adulthood,” based on the U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis (Br J Dermatol. 1994 Sep;131[3]:383-96).

This is the biggest epidemiologic survey ever to examine the 12-month prevalence and severity of AD around the world for both adults and children. Survey respondents included 172,627 adults aged 18 years and older, 34,212 adolescents aged 12-17 years, 54,806 children aged 2-11 years, and more than 12,000 infants.

Key findings from the study include the following:

• AD prevalence rates varied widely from country to country around the world, as well as by age groups (see graphic).
• The highest rate in adults was observed in China. South Korea had the highest rates in both children and adolescents. The top AD rates in infancy occurred in France and the United Kingdom.
• Rates across the age spectrum were consistently lowest in Israel and Switzerland.

“These kinds of patterns raise fascinating questions about the potential risk factors or protective factors that happen in different countries. There are some startling differences in terms of the different regions,” Dr. Silverberg observed. “Certain regions of the world really stand out as having much higher prevalences, particularly China and South Korea, and then as you get into the adult years, Brazil and Mexico, which I think are areas that, at least in the global atopic dermatitis epidemiology community, are not quite as well recognized as being hot spots for atopic dermatitis.”

Indeed, the 12-month prevalence rate of AD among adults was 14% in Mexico and 12% in Brazil, as compared with 13% in Saudi Arabia, 11% in Australia and Spain, 10% in Canada and the United Kingdom, and 9% in the United States.

The prevalence was generally lowest in infants, then jumped substantially within countries during the childhood years, declined slightly in adolescents, and then peaked in adulthood.

AD severity was assessed using PO-SCORAD, the Patient-Oriented Scoring AD measure. Most affected individuals had moderate AD as defined by a PO-SCORAD score of 25-50. Across the age spectrum, the highest proportion of infants with AD who had moderate disease was in China, with 72%. In Taiwan, 63% of children with AD had moderate disease, as did 68% of adolescents and an equal proportion of adults.

In the United Kingdom, 49% percent of infants with AD had severe disease, making that country the world leader in the youngest age group. Severe AD was most common among Turkish children, where 30% of kids with the skin disease had a PO-SCORAD score greater than 50. In Brazil, 31% of adolescents with AD had severe disease, the world’s highest rate in that age group. Among adults with AD, the world’s highest rate of severe disease was 25%, which was seen in the United States, Brazil, and Saudi Arabia.

Across the age spectrum, Japan had a consistently lower-end, overall, 12-month AD prevalence rate of 5%. Germany, Italy, and France had overall rates of 6%, 7%, and 8%, respectively. The rate was 9% in the United States and Canada, and it was 10% in Australia.

Dr. Silverberg performed validation analyses using the Patient-Oriented Eczema Measure (POEM) and diagnostic criteria similar to the earlier landmark International Study of Asthma and Allergies in Childhood, or ISAAC (Lancet. 1998 Apr 25;351[9111]:1225-32). This was a huge study that excluded the United States, leaving a hole in the epidemiologic picture of the disease that the new survey fills. The validation analyses were supportive of the main findings based on the U.K. Working Party criteria.

Dr. Silverberg reported serving as a consultant to Pfizer, which sponsored the global epidemiologic survey, as well as to roughly a dozen other pharmaceutical companies.

[email protected]

SOURCE: Silverberg JI. EADV Congress, Abstract FC01.01.

PARIS – A major worldwide survey of the 12-month prevalence of atopic dermatitis (AD) across the course of life provides new insights into global disease trends, Jonathan I. Silverberg, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Among the most important takeaways from this Internet-based survey of more than 273,645 infants, children, and adults in 18 countries across five continents conducted in 2017 was that “global atopic dermatitis prevalence appears to be higher in adults, at 10%, than in younger cohorts, where it’s 4%-8%, which I think is quite provocative and requires further study and confirmation,” said Dr. Silverberg, a dermatologist at Northwestern University in Chicago.

“Let’s keep in mind that there’s this accepted dogma in the literature than atopic dermatitis is somehow only a childhood disorder – it doesn’t affect adults. Well, these data tell a very different story because we’re actually seeing overall highest prevalences throughout the world occurring in adulthood,” based on the U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis (Br J Dermatol. 1994 Sep;131[3]:383-96).

This is the biggest epidemiologic survey ever to examine the 12-month prevalence and severity of AD around the world for both adults and children. Survey respondents included 172,627 adults aged 18 years and older, 34,212 adolescents aged 12-17 years, 54,806 children aged 2-11 years, and more than 12,000 infants.

Key findings from the study include the following:

• AD prevalence rates varied widely from country to country around the world, as well as by age groups (see graphic).
• The highest rate in adults was observed in China. South Korea had the highest rates in both children and adolescents. The top AD rates in infancy occurred in France and the United Kingdom.
• Rates across the age spectrum were consistently lowest in Israel and Switzerland.

“These kinds of patterns raise fascinating questions about the potential risk factors or protective factors that happen in different countries. There are some startling differences in terms of the different regions,” Dr. Silverberg observed. “Certain regions of the world really stand out as having much higher prevalences, particularly China and South Korea, and then as you get into the adult years, Brazil and Mexico, which I think are areas that, at least in the global atopic dermatitis epidemiology community, are not quite as well recognized as being hot spots for atopic dermatitis.”

Indeed, the 12-month prevalence rate of AD among adults was 14% in Mexico and 12% in Brazil, as compared with 13% in Saudi Arabia, 11% in Australia and Spain, 10% in Canada and the United Kingdom, and 9% in the United States.

The prevalence was generally lowest in infants, then jumped substantially within countries during the childhood years, declined slightly in adolescents, and then peaked in adulthood.

AD severity was assessed using PO-SCORAD, the Patient-Oriented Scoring AD measure. Most affected individuals had moderate AD as defined by a PO-SCORAD score of 25-50. Across the age spectrum, the highest proportion of infants with AD who had moderate disease was in China, with 72%. In Taiwan, 63% of children with AD had moderate disease, as did 68% of adolescents and an equal proportion of adults.

In the United Kingdom, 49% percent of infants with AD had severe disease, making that country the world leader in the youngest age group. Severe AD was most common among Turkish children, where 30% of kids with the skin disease had a PO-SCORAD score greater than 50. In Brazil, 31% of adolescents with AD had severe disease, the world’s highest rate in that age group. Among adults with AD, the world’s highest rate of severe disease was 25%, which was seen in the United States, Brazil, and Saudi Arabia.

Across the age spectrum, Japan had a consistently lower-end, overall, 12-month AD prevalence rate of 5%. Germany, Italy, and France had overall rates of 6%, 7%, and 8%, respectively. The rate was 9% in the United States and Canada, and it was 10% in Australia.

Dr. Silverberg performed validation analyses using the Patient-Oriented Eczema Measure (POEM) and diagnostic criteria similar to the earlier landmark International Study of Asthma and Allergies in Childhood, or ISAAC (Lancet. 1998 Apr 25;351[9111]:1225-32). This was a huge study that excluded the United States, leaving a hole in the epidemiologic picture of the disease that the new survey fills. The validation analyses were supportive of the main findings based on the U.K. Working Party criteria.

Dr. Silverberg reported serving as a consultant to Pfizer, which sponsored the global epidemiologic survey, as well as to roughly a dozen other pharmaceutical companies.

[email protected]

SOURCE: Silverberg JI. EADV Congress, Abstract FC01.01.

PARIS – A major worldwide survey of the 12-month prevalence of atopic dermatitis (AD) across the course of life provides new insights into global disease trends, Jonathan I. Silverberg, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Among the most important takeaways from this Internet-based survey of more than 273,645 infants, children, and adults in 18 countries across five continents conducted in 2017 was that “global atopic dermatitis prevalence appears to be higher in adults, at 10%, than in younger cohorts, where it’s 4%-8%, which I think is quite provocative and requires further study and confirmation,” said Dr. Silverberg, a dermatologist at Northwestern University in Chicago.

“Let’s keep in mind that there’s this accepted dogma in the literature than atopic dermatitis is somehow only a childhood disorder – it doesn’t affect adults. Well, these data tell a very different story because we’re actually seeing overall highest prevalences throughout the world occurring in adulthood,” based on the U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis (Br J Dermatol. 1994 Sep;131[3]:383-96).

This is the biggest epidemiologic survey ever to examine the 12-month prevalence and severity of AD around the world for both adults and children. Survey respondents included 172,627 adults aged 18 years and older, 34,212 adolescents aged 12-17 years, 54,806 children aged 2-11 years, and more than 12,000 infants.

Key findings from the study include the following:

• AD prevalence rates varied widely from country to country around the world, as well as by age groups (see graphic).
• The highest rate in adults was observed in China. South Korea had the highest rates in both children and adolescents. The top AD rates in infancy occurred in France and the United Kingdom.
• Rates across the age spectrum were consistently lowest in Israel and Switzerland.

“These kinds of patterns raise fascinating questions about the potential risk factors or protective factors that happen in different countries. There are some startling differences in terms of the different regions,” Dr. Silverberg observed. “Certain regions of the world really stand out as having much higher prevalences, particularly China and South Korea, and then as you get into the adult years, Brazil and Mexico, which I think are areas that, at least in the global atopic dermatitis epidemiology community, are not quite as well recognized as being hot spots for atopic dermatitis.”

Indeed, the 12-month prevalence rate of AD among adults was 14% in Mexico and 12% in Brazil, as compared with 13% in Saudi Arabia, 11% in Australia and Spain, 10% in Canada and the United Kingdom, and 9% in the United States.

The prevalence was generally lowest in infants, then jumped substantially within countries during the childhood years, declined slightly in adolescents, and then peaked in adulthood.

AD severity was assessed using PO-SCORAD, the Patient-Oriented Scoring AD measure. Most affected individuals had moderate AD as defined by a PO-SCORAD score of 25-50. Across the age spectrum, the highest proportion of infants with AD who had moderate disease was in China, with 72%. In Taiwan, 63% of children with AD had moderate disease, as did 68% of adolescents and an equal proportion of adults.

In the United Kingdom, 49% percent of infants with AD had severe disease, making that country the world leader in the youngest age group. Severe AD was most common among Turkish children, where 30% of kids with the skin disease had a PO-SCORAD score greater than 50. In Brazil, 31% of adolescents with AD had severe disease, the world’s highest rate in that age group. Among adults with AD, the world’s highest rate of severe disease was 25%, which was seen in the United States, Brazil, and Saudi Arabia.

Across the age spectrum, Japan had a consistently lower-end, overall, 12-month AD prevalence rate of 5%. Germany, Italy, and France had overall rates of 6%, 7%, and 8%, respectively. The rate was 9% in the United States and Canada, and it was 10% in Australia.

Dr. Silverberg performed validation analyses using the Patient-Oriented Eczema Measure (POEM) and diagnostic criteria similar to the earlier landmark International Study of Asthma and Allergies in Childhood, or ISAAC (Lancet. 1998 Apr 25;351[9111]:1225-32). This was a huge study that excluded the United States, leaving a hole in the epidemiologic picture of the disease that the new survey fills. The validation analyses were supportive of the main findings based on the U.K. Working Party criteria.

Dr. Silverberg reported serving as a consultant to Pfizer, which sponsored the global epidemiologic survey, as well as to roughly a dozen other pharmaceutical companies.

[email protected]

SOURCE: Silverberg JI. EADV Congress, Abstract FC01.01.

Whole-body cryotherapy (WBC) can lead to cold burns in some circumstances, according to a case report by Mackenzie O’Connor and her colleagues in the department of dermatology and cutaneous biology at Thomas Jefferson University, Philadelphia.

jacoblund/Getty Images

In the report, they describe the case of a 71-year-old man who presented with a cold burn injury a day after a WBC session. These treatments typically involve sessions of 2-5 minutes, in a chamber that is cooled down to –100°C to –140°C.

The likely cause in this case was a nozzle malfunction that caused liquid nitrogen to come in direct contact with the patient’s skin for a prolonged period of time (less than 1 minute), causing stinging and pain, followed by redness and blistering of the skin. The patient had received four WBC treatments previously for arthritis and back pain, with no adverse effects. In addition to ibuprofen, he was treated with systemic steroids, topical corticosteroids, and silver sulfadiazine cream.

Despite claims that WBC can aid muscle recovery and alleviate joint pain, and can improve skin health, and is increasingly available in spas and other sites, the Food and Drug Administration has not approved the procedure for treatment of any medical conditions, the researchers noted (JAAD Case Rep. 2019;5[1]:29-30). They also referred to a 2015 Cochrane review, which found insufficient evidence that WBC treatment is beneficial for muscle recovery in active young adult men.

[email protected]

Whole-body cryotherapy (WBC) can lead to cold burns in some circumstances, according to a case report by Mackenzie O’Connor and her colleagues in the department of dermatology and cutaneous biology at Thomas Jefferson University, Philadelphia.

jacoblund/Getty Images

In the report, they describe the case of a 71-year-old man who presented with a cold burn injury a day after a WBC session. These treatments typically involve sessions of 2-5 minutes, in a chamber that is cooled down to –100°C to –140°C.

The likely cause in this case was a nozzle malfunction that caused liquid nitrogen to come in direct contact with the patient’s skin for a prolonged period of time (less than 1 minute), causing stinging and pain, followed by redness and blistering of the skin. The patient had received four WBC treatments previously for arthritis and back pain, with no adverse effects. In addition to ibuprofen, he was treated with systemic steroids, topical corticosteroids, and silver sulfadiazine cream.

Despite claims that WBC can aid muscle recovery and alleviate joint pain, and can improve skin health, and is increasingly available in spas and other sites, the Food and Drug Administration has not approved the procedure for treatment of any medical conditions, the researchers noted (JAAD Case Rep. 2019;5[1]:29-30). They also referred to a 2015 Cochrane review, which found insufficient evidence that WBC treatment is beneficial for muscle recovery in active young adult men.

[email protected]

Whole-body cryotherapy (WBC) can lead to cold burns in some circumstances, according to a case report by Mackenzie O’Connor and her colleagues in the department of dermatology and cutaneous biology at Thomas Jefferson University, Philadelphia.

jacoblund/Getty Images

In the report, they describe the case of a 71-year-old man who presented with a cold burn injury a day after a WBC session. These treatments typically involve sessions of 2-5 minutes, in a chamber that is cooled down to –100°C to –140°C.

The likely cause in this case was a nozzle malfunction that caused liquid nitrogen to come in direct contact with the patient’s skin for a prolonged period of time (less than 1 minute), causing stinging and pain, followed by redness and blistering of the skin. The patient had received four WBC treatments previously for arthritis and back pain, with no adverse effects. In addition to ibuprofen, he was treated with systemic steroids, topical corticosteroids, and silver sulfadiazine cream.

Despite claims that WBC can aid muscle recovery and alleviate joint pain, and can improve skin health, and is increasingly available in spas and other sites, the Food and Drug Administration has not approved the procedure for treatment of any medical conditions, the researchers noted (JAAD Case Rep. 2019;5[1]:29-30). They also referred to a 2015 Cochrane review, which found insufficient evidence that WBC treatment is beneficial for muscle recovery in active young adult men.

[email protected]

HIV-associated neuromyelitis optica spectrum disorder (NMOSD) is a recently recognized entity and high index of suspicion is needed to diagnose these patients, according to Thomas Mathew, MD, and his colleagues at St. John’s Medical College Hospital, Bengaluru, India.

grandeduc/Thinkstock

“NMOSD can be associated with a wide range of autoimmune diseases but clinicians rarely diagnose NMOSD in cases of HIV infection and HIV-associated NMOSD is rarely mentioned in the conventional classification of NMOSD,” they stated.

Dr. Mathew and his colleagues reported the results of a case study they made of six cases of HIV-NMOSD identified from the literature and 1 HIV-infected patient from a registry for NMOSD that they had established, which had a total of 25 patients with the condition.

There were four men and three women in the study, ranging from 8 years to 49 years of age. The duration of HIV infection in these patients ranged from newly detected to 15 years, according to the report, published in Multiple Sclerosis and Related Disorders (2019 Jan;27:289-93).

Optic neuritis followed by myelitis was the commonest presentation, occurring in five of the seven patients. Of these, six patients were assayed for anti–aquaporin 4 antibodies, which are considered a serological marker of neuromyelitis optica; three patients were positive and three were negative.

All patients received immunomodulatory treatment. Five of the seven patients had a poor recovery from acute attacks, but no patient had further relapses while on immunomodulatory treatment and antiretroviral therapy.

Dr. Mathew and his colleagues suggested that all patients with HIV infection presenting with optic neuritis or/and myelitis, should have their anti–aquaporin 4 antibody status checked and in all patients of NMOSD, HIV infection should be ruled out.

“Prognosis of these patients is variable; residual neurological deficits were common but treatment prevented further attacks. Increased awareness of this association will lead to earlier diagnosis, early treatment and prevention of disability,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Mathew T et al. Mult Scler Relat Disord. 2019 Jan;27:289-93.

HIV-associated neuromyelitis optica spectrum disorder (NMOSD) is a recently recognized entity and high index of suspicion is needed to diagnose these patients, according to Thomas Mathew, MD, and his colleagues at St. John’s Medical College Hospital, Bengaluru, India.

grandeduc/Thinkstock

“NMOSD can be associated with a wide range of autoimmune diseases but clinicians rarely diagnose NMOSD in cases of HIV infection and HIV-associated NMOSD is rarely mentioned in the conventional classification of NMOSD,” they stated.

Dr. Mathew and his colleagues reported the results of a case study they made of six cases of HIV-NMOSD identified from the literature and 1 HIV-infected patient from a registry for NMOSD that they had established, which had a total of 25 patients with the condition.

There were four men and three women in the study, ranging from 8 years to 49 years of age. The duration of HIV infection in these patients ranged from newly detected to 15 years, according to the report, published in Multiple Sclerosis and Related Disorders (2019 Jan;27:289-93).

Optic neuritis followed by myelitis was the commonest presentation, occurring in five of the seven patients. Of these, six patients were assayed for anti–aquaporin 4 antibodies, which are considered a serological marker of neuromyelitis optica; three patients were positive and three were negative.

All patients received immunomodulatory treatment. Five of the seven patients had a poor recovery from acute attacks, but no patient had further relapses while on immunomodulatory treatment and antiretroviral therapy.

Dr. Mathew and his colleagues suggested that all patients with HIV infection presenting with optic neuritis or/and myelitis, should have their anti–aquaporin 4 antibody status checked and in all patients of NMOSD, HIV infection should be ruled out.

“Prognosis of these patients is variable; residual neurological deficits were common but treatment prevented further attacks. Increased awareness of this association will lead to earlier diagnosis, early treatment and prevention of disability,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Mathew T et al. Mult Scler Relat Disord. 2019 Jan;27:289-93.

HIV-associated neuromyelitis optica spectrum disorder (NMOSD) is a recently recognized entity and high index of suspicion is needed to diagnose these patients, according to Thomas Mathew, MD, and his colleagues at St. John’s Medical College Hospital, Bengaluru, India.

grandeduc/Thinkstock

“NMOSD can be associated with a wide range of autoimmune diseases but clinicians rarely diagnose NMOSD in cases of HIV infection and HIV-associated NMOSD is rarely mentioned in the conventional classification of NMOSD,” they stated.

Dr. Mathew and his colleagues reported the results of a case study they made of six cases of HIV-NMOSD identified from the literature and 1 HIV-infected patient from a registry for NMOSD that they had established, which had a total of 25 patients with the condition.

There were four men and three women in the study, ranging from 8 years to 49 years of age. The duration of HIV infection in these patients ranged from newly detected to 15 years, according to the report, published in Multiple Sclerosis and Related Disorders (2019 Jan;27:289-93).

Optic neuritis followed by myelitis was the commonest presentation, occurring in five of the seven patients. Of these, six patients were assayed for anti–aquaporin 4 antibodies, which are considered a serological marker of neuromyelitis optica; three patients were positive and three were negative.

All patients received immunomodulatory treatment. Five of the seven patients had a poor recovery from acute attacks, but no patient had further relapses while on immunomodulatory treatment and antiretroviral therapy.

Dr. Mathew and his colleagues suggested that all patients with HIV infection presenting with optic neuritis or/and myelitis, should have their anti–aquaporin 4 antibody status checked and in all patients of NMOSD, HIV infection should be ruled out.

“Prognosis of these patients is variable; residual neurological deficits were common but treatment prevented further attacks. Increased awareness of this association will lead to earlier diagnosis, early treatment and prevention of disability,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Mathew T et al. Mult Scler Relat Disord. 2019 Jan;27:289-93.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Reprocessed duodenoscopes are more contaminated than expected, with up to 3% of samples testing positive for disease-causing bacteria including Escherichia coli and Staphylococcus aureus, according to an updated safety communication issued by the Food and Drug Administration on December 10.

“Because of the higher-than-expected contamination rates and to help protect patients from bacterial infections associated with the use of duodenoscopes, we have included in today’s safety communication updated recommendations regarding steps that health care providers can take to enhance duodenoscope reprocessing,” Jeff Shuren, MD, director of the Center for Devices and Radiological Health, wrote in the statement.

The FDA advised clinicians to follow additional cleaning measures including microbiological culturing, sterilization, use of a liquid chemical sterilant processing system, and repeated high-level disinfection beyond what is recommended by duodenoscope manufacturers.

The interim data cited in the safety communication come from postmarket surveillance studies conducted by duodenoscope manufacturers at the FDA’s request as part of the agency’s ongoing efforts to prevent patient infections caused by contaminated duodenoscopes. In addition to the positive tests for disease-causing bacteria, up to 3% of properly collected samples contained more than 100 colony-forming units of other organisms unlikely to cause infection. However, the presence of such organisms further highlights the failure of the current reprocessing protocol to adequately clean the devices, according to the FDA.

Dr. Shuren emphasized that the risk of infection from a duodenoscope for an individual patient remains low and that infection rates have declined in recent years in response to the FDA’s enhanced safety measures and stated that the agency remains “committed to enhancing the safety margin of procedures with reprocessed medical devices.”

Read the full safety communication here: https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm628020.htm.

Reprocessed duodenoscopes are more contaminated than expected, with up to 3% of samples testing positive for disease-causing bacteria including Escherichia coli and Staphylococcus aureus, according to an updated safety communication issued by the Food and Drug Administration on December 10.

“Because of the higher-than-expected contamination rates and to help protect patients from bacterial infections associated with the use of duodenoscopes, we have included in today’s safety communication updated recommendations regarding steps that health care providers can take to enhance duodenoscope reprocessing,” Jeff Shuren, MD, director of the Center for Devices and Radiological Health, wrote in the statement.

The FDA advised clinicians to follow additional cleaning measures including microbiological culturing, sterilization, use of a liquid chemical sterilant processing system, and repeated high-level disinfection beyond what is recommended by duodenoscope manufacturers.

The interim data cited in the safety communication come from postmarket surveillance studies conducted by duodenoscope manufacturers at the FDA’s request as part of the agency’s ongoing efforts to prevent patient infections caused by contaminated duodenoscopes. In addition to the positive tests for disease-causing bacteria, up to 3% of properly collected samples contained more than 100 colony-forming units of other organisms unlikely to cause infection. However, the presence of such organisms further highlights the failure of the current reprocessing protocol to adequately clean the devices, according to the FDA.

Dr. Shuren emphasized that the risk of infection from a duodenoscope for an individual patient remains low and that infection rates have declined in recent years in response to the FDA’s enhanced safety measures and stated that the agency remains “committed to enhancing the safety margin of procedures with reprocessed medical devices.”

Read the full safety communication here: https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm628020.htm.

Reprocessed duodenoscopes are more contaminated than expected, with up to 3% of samples testing positive for disease-causing bacteria including Escherichia coli and Staphylococcus aureus, according to an updated safety communication issued by the Food and Drug Administration on December 10.

“Because of the higher-than-expected contamination rates and to help protect patients from bacterial infections associated with the use of duodenoscopes, we have included in today’s safety communication updated recommendations regarding steps that health care providers can take to enhance duodenoscope reprocessing,” Jeff Shuren, MD, director of the Center for Devices and Radiological Health, wrote in the statement.

The FDA advised clinicians to follow additional cleaning measures including microbiological culturing, sterilization, use of a liquid chemical sterilant processing system, and repeated high-level disinfection beyond what is recommended by duodenoscope manufacturers.

The interim data cited in the safety communication come from postmarket surveillance studies conducted by duodenoscope manufacturers at the FDA’s request as part of the agency’s ongoing efforts to prevent patient infections caused by contaminated duodenoscopes. In addition to the positive tests for disease-causing bacteria, up to 3% of properly collected samples contained more than 100 colony-forming units of other organisms unlikely to cause infection. However, the presence of such organisms further highlights the failure of the current reprocessing protocol to adequately clean the devices, according to the FDA.

Dr. Shuren emphasized that the risk of infection from a duodenoscope for an individual patient remains low and that infection rates have declined in recent years in response to the FDA’s enhanced safety measures and stated that the agency remains “committed to enhancing the safety margin of procedures with reprocessed medical devices.”

Read the full safety communication here: https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm628020.htm.

It’s well known that overuse is an enormous problem in medicine, and when it comes to antibiotics, the problem is even more striking.

FotoMaximum/Thinkstock

“Half of all inpatient antibiotic use is inappropriate,” says Valerie Vaughn, MD, MSc, a hospitalist at the University of Michigan, Ann Arbor, and coauthor of a BMJ editorial about EHRs and antibiotic overuse.

“This has led to an increase in antibiotic-related adverse events (~20% of all hospitalized patients on antibiotics), Clostridium difficile infections (half a million infections and 29,000 deaths in U.S. annually), and resistant bacteria (which now account for nearly 12% of all bacterial infections, costing $2.2 billion annually).”

EHRs can be a tool to combat that trend – if they are well designed. Clinicians are influenced by the design of their electronic health record, Dr. Vaughn said. “Rather than leave its influence to chance, we should capitalize on what is known about design to promote appropriate testing and treatment through the EHR.” Hospitalists – integral to quality improvement – can have a role in making these changes.

“These improvements will be the most effective if behavioral economics and nudging are considered while designing,” Dr. Vaughn said. “For example, when creating order sets, list recommended options first and when possible make them the default,” she said. “This little change will greatly improve appropriate use.”

For every hour physicians spend on direct patient care, they spend another two with the EHR, Dr. Vaughn wrote. “Given this degree of attention, it is not surprising that the EHR influences physician behavior, especially the overuse of low-value medical care. … Displaying brand-name instead of generic options leads to more expensive prescribing. Allowing labs to be ordered recurrently increases unnecessary phlebotomy. Even individually listing inappropriate antibiotics (rather than grouping them) can make them more noticeable, resulting in more broad-spectrum use.”

“All hospitalists – and humans – are affected by knee-jerk responses. One of the most common in medicine is the urge to treat a positive culture or any positive test. Recognize this urge and resist!” she said. “Antibiotics may be the correct response, but clinicians should first think about whether treatment is necessary based on that patient’s symptoms and comorbidities. Resist the knee-jerk urge to give antibiotics for every positive culture.”
 

Reference

Vaughn VM et al. Thoughtless design of the electronic health record drives overuse, but purposeful design can nudge improved patient care. BMJ Qual Saf. 24 Mar 2018. doi: 10.1136/bmjqs-2017-007578.

It’s well known that overuse is an enormous problem in medicine, and when it comes to antibiotics, the problem is even more striking.

FotoMaximum/Thinkstock

“Half of all inpatient antibiotic use is inappropriate,” says Valerie Vaughn, MD, MSc, a hospitalist at the University of Michigan, Ann Arbor, and coauthor of a BMJ editorial about EHRs and antibiotic overuse.

“This has led to an increase in antibiotic-related adverse events (~20% of all hospitalized patients on antibiotics), Clostridium difficile infections (half a million infections and 29,000 deaths in U.S. annually), and resistant bacteria (which now account for nearly 12% of all bacterial infections, costing $2.2 billion annually).”

EHRs can be a tool to combat that trend – if they are well designed. Clinicians are influenced by the design of their electronic health record, Dr. Vaughn said. “Rather than leave its influence to chance, we should capitalize on what is known about design to promote appropriate testing and treatment through the EHR.” Hospitalists – integral to quality improvement – can have a role in making these changes.

“These improvements will be the most effective if behavioral economics and nudging are considered while designing,” Dr. Vaughn said. “For example, when creating order sets, list recommended options first and when possible make them the default,” she said. “This little change will greatly improve appropriate use.”

For every hour physicians spend on direct patient care, they spend another two with the EHR, Dr. Vaughn wrote. “Given this degree of attention, it is not surprising that the EHR influences physician behavior, especially the overuse of low-value medical care. … Displaying brand-name instead of generic options leads to more expensive prescribing. Allowing labs to be ordered recurrently increases unnecessary phlebotomy. Even individually listing inappropriate antibiotics (rather than grouping them) can make them more noticeable, resulting in more broad-spectrum use.”

“All hospitalists – and humans – are affected by knee-jerk responses. One of the most common in medicine is the urge to treat a positive culture or any positive test. Recognize this urge and resist!” she said. “Antibiotics may be the correct response, but clinicians should first think about whether treatment is necessary based on that patient’s symptoms and comorbidities. Resist the knee-jerk urge to give antibiotics for every positive culture.”
 

Reference

Vaughn VM et al. Thoughtless design of the electronic health record drives overuse, but purposeful design can nudge improved patient care. BMJ Qual Saf. 24 Mar 2018. doi: 10.1136/bmjqs-2017-007578.

It’s well known that overuse is an enormous problem in medicine, and when it comes to antibiotics, the problem is even more striking.

FotoMaximum/Thinkstock

“Half of all inpatient antibiotic use is inappropriate,” says Valerie Vaughn, MD, MSc, a hospitalist at the University of Michigan, Ann Arbor, and coauthor of a BMJ editorial about EHRs and antibiotic overuse.

“This has led to an increase in antibiotic-related adverse events (~20% of all hospitalized patients on antibiotics), Clostridium difficile infections (half a million infections and 29,000 deaths in U.S. annually), and resistant bacteria (which now account for nearly 12% of all bacterial infections, costing $2.2 billion annually).”

EHRs can be a tool to combat that trend – if they are well designed. Clinicians are influenced by the design of their electronic health record, Dr. Vaughn said. “Rather than leave its influence to chance, we should capitalize on what is known about design to promote appropriate testing and treatment through the EHR.” Hospitalists – integral to quality improvement – can have a role in making these changes.

“These improvements will be the most effective if behavioral economics and nudging are considered while designing,” Dr. Vaughn said. “For example, when creating order sets, list recommended options first and when possible make them the default,” she said. “This little change will greatly improve appropriate use.”

For every hour physicians spend on direct patient care, they spend another two with the EHR, Dr. Vaughn wrote. “Given this degree of attention, it is not surprising that the EHR influences physician behavior, especially the overuse of low-value medical care. … Displaying brand-name instead of generic options leads to more expensive prescribing. Allowing labs to be ordered recurrently increases unnecessary phlebotomy. Even individually listing inappropriate antibiotics (rather than grouping them) can make them more noticeable, resulting in more broad-spectrum use.”

“All hospitalists – and humans – are affected by knee-jerk responses. One of the most common in medicine is the urge to treat a positive culture or any positive test. Recognize this urge and resist!” she said. “Antibiotics may be the correct response, but clinicians should first think about whether treatment is necessary based on that patient’s symptoms and comorbidities. Resist the knee-jerk urge to give antibiotics for every positive culture.”
 

Reference

Vaughn VM et al. Thoughtless design of the electronic health record drives overuse, but purposeful design can nudge improved patient care. BMJ Qual Saf. 24 Mar 2018. doi: 10.1136/bmjqs-2017-007578.

Serum biomarkers may enable a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), according to results from a recent study.

Nephron/Wikimedia/Creative Commons License

An algorithm created by the investigators distinguished NAFLD patients with advanced liver fibrosis from those with mild to moderate fibrosis, reported lead author Rohit Loomba, MD, of the University of California at San Diego and his colleagues.

“Liver biopsy is currently the gold standard for diagnosing NASH [nonalcoholic steatohepatitis] and staging liver fibrosis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, it is a costly and invasive procedure with an all-cause mortality risk of approximately 0.2%. Liver biopsy typically samples only 1/50,000th of the organ, and it is liable to sampling error with an error rate of 25% for diagnosis of hepatic fibrosis.”

Existing serum-based tests are reliable for diagnosing nonfibrotic NAFLD, but they may misdiagnosis patients with advanced fibrosis. Although imaging-based techniques may provide better diagnostic accuracy, some are available only for subgroups of patients, while others come with a high financial burden. Diagnostic shortcomings may have a major effect on patient outcomes, particularly when risk groups are considered.

“Fibrosis stages F3 and F4 (advanced fibrosis) are primary predictors of liver-related morbidity and mortality, with 11%-22% of NASH patients reported to have advanced fibrosis,” the investigators noted.

The investigators therefore aimed to distinguish such high-risk NAFLD patients from those with mild or moderate liver fibrosis. Three biomarkers were included: hyaluronic acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP-1), and alpha₂-macroglobulin (A2M). Each biomarker has documented associations with liver fibrosis. For instance, higher A2M concentrations inhibit fibrinolysis, HA is associated with excessive extracellular matrix and fibrotic tissue, and TIMP-1 is a known liver fibrosis marker and inhibitor of extracellular matrix degradation. The relative strengths of each in detecting advanced liver fibrosis was determined through an algorithm.

The investigators relied on archived serum samples from Duke University, Durham, N.C., (n = 792) and University of California at San Diego (n = 244) that were collected within 11 days of liver biopsy. Biopsies were performed with 15- to 16-gauge needles using at least eight portal tracts, and these samples were used to diagnose NAFLD. Patients with alcoholic liver disease or hepatitis C virus were excluded.

Algorithm training was based on serum measurements from 396 patients treated at Duke University. Samples were divided into mild to moderate (F0-F2) or advanced (F3-F4) fibrosis and split into 10 subsets. The logical regression model was trained on nine subsets and tested on the 10th, with iterations 10 times through this sequence until all 10 samples were tested. This process was repeated 10,000 times. Using the median coefficients from 100,000 logistical regression models, the samples were scored using the algorithm from 0 to 100, with higher numbers representing more advanced fibrosis, and the relative weights of each biomarker measurement were determined.

A noninferiority protocol was used to validate the algorithm, through which the area under the receiver operating characteristic (AUROC) curve was calculated. The AUROC curve of the validation samples was 0.856, with 0.5 being the score for a random algorithm. The algorithm correctly classified 90.0% of F0 cases, 75.0% of F1 cases, 53.8% of F2 cases, 77.4% of F3 cases, and 94.4% of F4 cases. The sensitivity was 79.7% and the specificity was 75.7%.

The algorithm was superior to Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in two validation cohorts. In a combination of validation cohorts, the algorithm correctly identified 79.5% of F3-F4 patients, compared with rates of 25.8% and 28.0% from FIB-4 and NFS, respectively. The investigators noted that the algorithm was unaffected by sex or age. In contrast, FIB-4 is biased toward females, and both FIB-4 and NFS are less accurate with patients aged 35 years or younger.

“Performance of the training and validation sets was robust and well matched, enabling the reliable differentiation of NAFLD patients with and without advanced fibrosis,” the investigators concluded.

The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.

SOURCE: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.

Serum biomarkers may enable a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), according to results from a recent study.

Nephron/Wikimedia/Creative Commons License

An algorithm created by the investigators distinguished NAFLD patients with advanced liver fibrosis from those with mild to moderate fibrosis, reported lead author Rohit Loomba, MD, of the University of California at San Diego and his colleagues.

“Liver biopsy is currently the gold standard for diagnosing NASH [nonalcoholic steatohepatitis] and staging liver fibrosis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, it is a costly and invasive procedure with an all-cause mortality risk of approximately 0.2%. Liver biopsy typically samples only 1/50,000th of the organ, and it is liable to sampling error with an error rate of 25% for diagnosis of hepatic fibrosis.”

Existing serum-based tests are reliable for diagnosing nonfibrotic NAFLD, but they may misdiagnosis patients with advanced fibrosis. Although imaging-based techniques may provide better diagnostic accuracy, some are available only for subgroups of patients, while others come with a high financial burden. Diagnostic shortcomings may have a major effect on patient outcomes, particularly when risk groups are considered.

“Fibrosis stages F3 and F4 (advanced fibrosis) are primary predictors of liver-related morbidity and mortality, with 11%-22% of NASH patients reported to have advanced fibrosis,” the investigators noted.

The investigators therefore aimed to distinguish such high-risk NAFLD patients from those with mild or moderate liver fibrosis. Three biomarkers were included: hyaluronic acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP-1), and alpha₂-macroglobulin (A2M). Each biomarker has documented associations with liver fibrosis. For instance, higher A2M concentrations inhibit fibrinolysis, HA is associated with excessive extracellular matrix and fibrotic tissue, and TIMP-1 is a known liver fibrosis marker and inhibitor of extracellular matrix degradation. The relative strengths of each in detecting advanced liver fibrosis was determined through an algorithm.

The investigators relied on archived serum samples from Duke University, Durham, N.C., (n = 792) and University of California at San Diego (n = 244) that were collected within 11 days of liver biopsy. Biopsies were performed with 15- to 16-gauge needles using at least eight portal tracts, and these samples were used to diagnose NAFLD. Patients with alcoholic liver disease or hepatitis C virus were excluded.

Algorithm training was based on serum measurements from 396 patients treated at Duke University. Samples were divided into mild to moderate (F0-F2) or advanced (F3-F4) fibrosis and split into 10 subsets. The logical regression model was trained on nine subsets and tested on the 10th, with iterations 10 times through this sequence until all 10 samples were tested. This process was repeated 10,000 times. Using the median coefficients from 100,000 logistical regression models, the samples were scored using the algorithm from 0 to 100, with higher numbers representing more advanced fibrosis, and the relative weights of each biomarker measurement were determined.

A noninferiority protocol was used to validate the algorithm, through which the area under the receiver operating characteristic (AUROC) curve was calculated. The AUROC curve of the validation samples was 0.856, with 0.5 being the score for a random algorithm. The algorithm correctly classified 90.0% of F0 cases, 75.0% of F1 cases, 53.8% of F2 cases, 77.4% of F3 cases, and 94.4% of F4 cases. The sensitivity was 79.7% and the specificity was 75.7%.

The algorithm was superior to Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in two validation cohorts. In a combination of validation cohorts, the algorithm correctly identified 79.5% of F3-F4 patients, compared with rates of 25.8% and 28.0% from FIB-4 and NFS, respectively. The investigators noted that the algorithm was unaffected by sex or age. In contrast, FIB-4 is biased toward females, and both FIB-4 and NFS are less accurate with patients aged 35 years or younger.

“Performance of the training and validation sets was robust and well matched, enabling the reliable differentiation of NAFLD patients with and without advanced fibrosis,” the investigators concluded.

The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.

SOURCE: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.

Serum biomarkers may enable a noninvasive method of detecting advanced hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), according to results from a recent study.

Nephron/Wikimedia/Creative Commons License

An algorithm created by the investigators distinguished NAFLD patients with advanced liver fibrosis from those with mild to moderate fibrosis, reported lead author Rohit Loomba, MD, of the University of California at San Diego and his colleagues.

“Liver biopsy is currently the gold standard for diagnosing NASH [nonalcoholic steatohepatitis] and staging liver fibrosis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, it is a costly and invasive procedure with an all-cause mortality risk of approximately 0.2%. Liver biopsy typically samples only 1/50,000th of the organ, and it is liable to sampling error with an error rate of 25% for diagnosis of hepatic fibrosis.”

Existing serum-based tests are reliable for diagnosing nonfibrotic NAFLD, but they may misdiagnosis patients with advanced fibrosis. Although imaging-based techniques may provide better diagnostic accuracy, some are available only for subgroups of patients, while others come with a high financial burden. Diagnostic shortcomings may have a major effect on patient outcomes, particularly when risk groups are considered.

“Fibrosis stages F3 and F4 (advanced fibrosis) are primary predictors of liver-related morbidity and mortality, with 11%-22% of NASH patients reported to have advanced fibrosis,” the investigators noted.

The investigators therefore aimed to distinguish such high-risk NAFLD patients from those with mild or moderate liver fibrosis. Three biomarkers were included: hyaluronic acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP-1), and alpha₂-macroglobulin (A2M). Each biomarker has documented associations with liver fibrosis. For instance, higher A2M concentrations inhibit fibrinolysis, HA is associated with excessive extracellular matrix and fibrotic tissue, and TIMP-1 is a known liver fibrosis marker and inhibitor of extracellular matrix degradation. The relative strengths of each in detecting advanced liver fibrosis was determined through an algorithm.

The investigators relied on archived serum samples from Duke University, Durham, N.C., (n = 792) and University of California at San Diego (n = 244) that were collected within 11 days of liver biopsy. Biopsies were performed with 15- to 16-gauge needles using at least eight portal tracts, and these samples were used to diagnose NAFLD. Patients with alcoholic liver disease or hepatitis C virus were excluded.

Algorithm training was based on serum measurements from 396 patients treated at Duke University. Samples were divided into mild to moderate (F0-F2) or advanced (F3-F4) fibrosis and split into 10 subsets. The logical regression model was trained on nine subsets and tested on the 10th, with iterations 10 times through this sequence until all 10 samples were tested. This process was repeated 10,000 times. Using the median coefficients from 100,000 logistical regression models, the samples were scored using the algorithm from 0 to 100, with higher numbers representing more advanced fibrosis, and the relative weights of each biomarker measurement were determined.

A noninferiority protocol was used to validate the algorithm, through which the area under the receiver operating characteristic (AUROC) curve was calculated. The AUROC curve of the validation samples was 0.856, with 0.5 being the score for a random algorithm. The algorithm correctly classified 90.0% of F0 cases, 75.0% of F1 cases, 53.8% of F2 cases, 77.4% of F3 cases, and 94.4% of F4 cases. The sensitivity was 79.7% and the specificity was 75.7%.

The algorithm was superior to Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in two validation cohorts. In a combination of validation cohorts, the algorithm correctly identified 79.5% of F3-F4 patients, compared with rates of 25.8% and 28.0% from FIB-4 and NFS, respectively. The investigators noted that the algorithm was unaffected by sex or age. In contrast, FIB-4 is biased toward females, and both FIB-4 and NFS are less accurate with patients aged 35 years or younger.

“Performance of the training and validation sets was robust and well matched, enabling the reliable differentiation of NAFLD patients with and without advanced fibrosis,” the investigators concluded.

The study was supported by Prometheus Laboratories. Authors not employed by Prometheus Laboratories were employed by Duke University or the University of California, San Diego; each institution received funding from Prometheus Laboratories.

SOURCE: Loomba R et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.004.

This week, the American Heart Association says that statins’ benefits far outweigh the risks, a smartphone app is nearly as good as an ECG at diagnosing STEMI, stroke thrombolysis appears safe in patients prone to GI bleeding, and a new strategy for pausing DOAC therapy works in A-fib patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts
 

This week, the American Heart Association says that statins’ benefits far outweigh the risks, a smartphone app is nearly as good as an ECG at diagnosing STEMI, stroke thrombolysis appears safe in patients prone to GI bleeding, and a new strategy for pausing DOAC therapy works in A-fib patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts
 

This week, the American Heart Association says that statins’ benefits far outweigh the risks, a smartphone app is nearly as good as an ECG at diagnosing STEMI, stroke thrombolysis appears safe in patients prone to GI bleeding, and a new strategy for pausing DOAC therapy works in A-fib patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts