Lung function appears to continue to decline even decades after smoking cessation, according to new data from the National Heart, Lung, and Blood Institute Pooled Cohort Study. Compared with never-smokers, former smokers had a decline in forced expiratory volume in 1 second (FEV₁) about 20% as severe as current smokers, but nevertheless higher than never-smokers. Low-intensity smokers also fared worse than never-smokers, suggesting that no amount of smoke exposure should be considered safe.

bilderbox/fotolia.com

The increased decline occurred even decades after smoking cessation, according to the study published in Lancet Respiratory Medicine, which was led by Elizabeth Oelsner, MD, MPH, of Columbia University, New York. Smoking prevalence has decreased from 42% to 16% in the past 50 years, and many smokers report that they smoke fewer cigarettes per day, from an average of 21 to 14, according to the authors. Despite those trends, the prevalence of chronic obstructive pulmonary disease has continued to increase, and is now the third-leading cause of death worldwide.

A meta-analysis of 47 studies and 88,887 adults found no association between smoking and FEV₁ decline, but many of the studies were small or focused on nonrepresentative populations, and they used variably standardized spirometry.

The study pooled data from nine individual U.S. cohorts, with 25,352 participants recruited during 1983-2016. Subjects included those who underwent at least two prebronchodilator spirometry tests following American Thoracic Society standards. After adjustment, former smokers had increased FEV₁ decline of 1.82 mL/year (P less than .0001), compared with never-smokers. Current smokers had an increased decline of 9.21 mL/year (P less than .0001).

Even after decades of abstinence, the effects of smoking appeared to linger: 20-30 years later, FEV₁ loss was accelerated by 2.50 mL/year (P less than .0001), and by 0.93 mL/year (P = .0104) after 30 years, compared with never-smokers.

Even low-intensity smokers (cumulative less than 10 pack-years) had an significantly accelerated FEV₁ decline (0.87 mL; P = .0153).

The researchers also found a relationship between FEV₁ decline and intensity of current smoking: Those smoking fewer than 5 cigarettes per day had a lower decline than those smoking 30 or more (7.65 mL; 95% confidence interval, 6.21-9.09 vs. 11.24 mL; 95% CI, 9.86-12.62).

The study is limited by the fact that smoking status and daily tobacco reporting were self-reported, which could result in information bias.

The study was funded by the National Institutes of Health, National Heart Lung and Blood Institute, and U.S. Environmental Protection Agency. The authors report personal fees, consultancy fees, or grants from a wide variety of pharmaceutical companies.
 

SOURCE: Oelsner EC et al. Lancet Respir Med. 2019 Oct 9. doi: 10.1016/S2213-2600(19)30276-0.

Lung function appears to continue to decline even decades after smoking cessation, according to new data from the National Heart, Lung, and Blood Institute Pooled Cohort Study. Compared with never-smokers, former smokers had a decline in forced expiratory volume in 1 second (FEV₁) about 20% as severe as current smokers, but nevertheless higher than never-smokers. Low-intensity smokers also fared worse than never-smokers, suggesting that no amount of smoke exposure should be considered safe.

bilderbox/fotolia.com

The increased decline occurred even decades after smoking cessation, according to the study published in Lancet Respiratory Medicine, which was led by Elizabeth Oelsner, MD, MPH, of Columbia University, New York. Smoking prevalence has decreased from 42% to 16% in the past 50 years, and many smokers report that they smoke fewer cigarettes per day, from an average of 21 to 14, according to the authors. Despite those trends, the prevalence of chronic obstructive pulmonary disease has continued to increase, and is now the third-leading cause of death worldwide.

A meta-analysis of 47 studies and 88,887 adults found no association between smoking and FEV₁ decline, but many of the studies were small or focused on nonrepresentative populations, and they used variably standardized spirometry.

The study pooled data from nine individual U.S. cohorts, with 25,352 participants recruited during 1983-2016. Subjects included those who underwent at least two prebronchodilator spirometry tests following American Thoracic Society standards. After adjustment, former smokers had increased FEV₁ decline of 1.82 mL/year (P less than .0001), compared with never-smokers. Current smokers had an increased decline of 9.21 mL/year (P less than .0001).

Even after decades of abstinence, the effects of smoking appeared to linger: 20-30 years later, FEV₁ loss was accelerated by 2.50 mL/year (P less than .0001), and by 0.93 mL/year (P = .0104) after 30 years, compared with never-smokers.

Even low-intensity smokers (cumulative less than 10 pack-years) had an significantly accelerated FEV₁ decline (0.87 mL; P = .0153).

The researchers also found a relationship between FEV₁ decline and intensity of current smoking: Those smoking fewer than 5 cigarettes per day had a lower decline than those smoking 30 or more (7.65 mL; 95% confidence interval, 6.21-9.09 vs. 11.24 mL; 95% CI, 9.86-12.62).

The study is limited by the fact that smoking status and daily tobacco reporting were self-reported, which could result in information bias.

The study was funded by the National Institutes of Health, National Heart Lung and Blood Institute, and U.S. Environmental Protection Agency. The authors report personal fees, consultancy fees, or grants from a wide variety of pharmaceutical companies.
 

SOURCE: Oelsner EC et al. Lancet Respir Med. 2019 Oct 9. doi: 10.1016/S2213-2600(19)30276-0.

Lung function appears to continue to decline even decades after smoking cessation, according to new data from the National Heart, Lung, and Blood Institute Pooled Cohort Study. Compared with never-smokers, former smokers had a decline in forced expiratory volume in 1 second (FEV₁) about 20% as severe as current smokers, but nevertheless higher than never-smokers. Low-intensity smokers also fared worse than never-smokers, suggesting that no amount of smoke exposure should be considered safe.

bilderbox/fotolia.com

The increased decline occurred even decades after smoking cessation, according to the study published in Lancet Respiratory Medicine, which was led by Elizabeth Oelsner, MD, MPH, of Columbia University, New York. Smoking prevalence has decreased from 42% to 16% in the past 50 years, and many smokers report that they smoke fewer cigarettes per day, from an average of 21 to 14, according to the authors. Despite those trends, the prevalence of chronic obstructive pulmonary disease has continued to increase, and is now the third-leading cause of death worldwide.

A meta-analysis of 47 studies and 88,887 adults found no association between smoking and FEV₁ decline, but many of the studies were small or focused on nonrepresentative populations, and they used variably standardized spirometry.

The study pooled data from nine individual U.S. cohorts, with 25,352 participants recruited during 1983-2016. Subjects included those who underwent at least two prebronchodilator spirometry tests following American Thoracic Society standards. After adjustment, former smokers had increased FEV₁ decline of 1.82 mL/year (P less than .0001), compared with never-smokers. Current smokers had an increased decline of 9.21 mL/year (P less than .0001).

Even after decades of abstinence, the effects of smoking appeared to linger: 20-30 years later, FEV₁ loss was accelerated by 2.50 mL/year (P less than .0001), and by 0.93 mL/year (P = .0104) after 30 years, compared with never-smokers.

Even low-intensity smokers (cumulative less than 10 pack-years) had an significantly accelerated FEV₁ decline (0.87 mL; P = .0153).

The researchers also found a relationship between FEV₁ decline and intensity of current smoking: Those smoking fewer than 5 cigarettes per day had a lower decline than those smoking 30 or more (7.65 mL; 95% confidence interval, 6.21-9.09 vs. 11.24 mL; 95% CI, 9.86-12.62).

The study is limited by the fact that smoking status and daily tobacco reporting were self-reported, which could result in information bias.

The study was funded by the National Institutes of Health, National Heart Lung and Blood Institute, and U.S. Environmental Protection Agency. The authors report personal fees, consultancy fees, or grants from a wide variety of pharmaceutical companies.
 

SOURCE: Oelsner EC et al. Lancet Respir Med. 2019 Oct 9. doi: 10.1016/S2213-2600(19)30276-0.

Type 2 diabetes patients with binge-eating psychopathology had worse glycemic control than did type 2 diabetes patients without eating disorders, but weight may be a modifying factor, according to a study of 70 outpatients with type 2 diabetes.

“Although the comorbidity of an ED [eating disorder] and T2DM [type 2 diabetes mellitus] has been observed across studies, the impact of this association on the clinical control of diabetes has been less consistent,” wrote Marcello Papelbaum, MD, of the State Institute of Diabetes and Endocrinology, Rio de Janeiro and colleagues.

In an exploratory study published in the Journal of Eating Disorders, the researchers assessed consecutive diabetes patients at a single center. The patients were aged 18-65 years, 77% were women, and 50% were obese. Glycemic control of diabetes was assessed measuring the levels of fasting blood glucose (FBG) and hemoglobin A_1c. A total of 14 patients had an eating disorder, and 7 of them had binge eating disorder (BED). The BED patients were combined with three bulimic patients and four patients with subclinical BED and classified as binge-eating related ED.

Although FBG and HbA_1c were significantly worse in patients with an eating disorder, compared with patients with normal eating patterns, the significance disappeared when body mass index (BMI) was added to the regression model. “Specifically, normal-BMI individuals exhibited a rate of ED of 8%, contrasted with a 26% prevalence of ED in obese patients,” the authors stated.

The findings were limited by the exploratory study design, small sample size, and lack of controlling for multiple variables, the researchers noted.

However, “although the objective negative clinical impact of an ED on type 2 diabetes control is yet to be confirmed, is possible to speculate that the remission of binge episodes could play a major role in diabetes treatment,” they said.

The researchers had no financial conflicts to disclose.
 

SOURCE: Papelbaum M et al. J Eat Disord. 2019 Sep 6. doi: 10.1186/s40337-019-0260-4.

Type 2 diabetes patients with binge-eating psychopathology had worse glycemic control than did type 2 diabetes patients without eating disorders, but weight may be a modifying factor, according to a study of 70 outpatients with type 2 diabetes.

“Although the comorbidity of an ED [eating disorder] and T2DM [type 2 diabetes mellitus] has been observed across studies, the impact of this association on the clinical control of diabetes has been less consistent,” wrote Marcello Papelbaum, MD, of the State Institute of Diabetes and Endocrinology, Rio de Janeiro and colleagues.

In an exploratory study published in the Journal of Eating Disorders, the researchers assessed consecutive diabetes patients at a single center. The patients were aged 18-65 years, 77% were women, and 50% were obese. Glycemic control of diabetes was assessed measuring the levels of fasting blood glucose (FBG) and hemoglobin A_1c. A total of 14 patients had an eating disorder, and 7 of them had binge eating disorder (BED). The BED patients were combined with three bulimic patients and four patients with subclinical BED and classified as binge-eating related ED.

Although FBG and HbA_1c were significantly worse in patients with an eating disorder, compared with patients with normal eating patterns, the significance disappeared when body mass index (BMI) was added to the regression model. “Specifically, normal-BMI individuals exhibited a rate of ED of 8%, contrasted with a 26% prevalence of ED in obese patients,” the authors stated.

The findings were limited by the exploratory study design, small sample size, and lack of controlling for multiple variables, the researchers noted.

However, “although the objective negative clinical impact of an ED on type 2 diabetes control is yet to be confirmed, is possible to speculate that the remission of binge episodes could play a major role in diabetes treatment,” they said.

The researchers had no financial conflicts to disclose.
 

SOURCE: Papelbaum M et al. J Eat Disord. 2019 Sep 6. doi: 10.1186/s40337-019-0260-4.

Type 2 diabetes patients with binge-eating psychopathology had worse glycemic control than did type 2 diabetes patients without eating disorders, but weight may be a modifying factor, according to a study of 70 outpatients with type 2 diabetes.

“Although the comorbidity of an ED [eating disorder] and T2DM [type 2 diabetes mellitus] has been observed across studies, the impact of this association on the clinical control of diabetes has been less consistent,” wrote Marcello Papelbaum, MD, of the State Institute of Diabetes and Endocrinology, Rio de Janeiro and colleagues.

In an exploratory study published in the Journal of Eating Disorders, the researchers assessed consecutive diabetes patients at a single center. The patients were aged 18-65 years, 77% were women, and 50% were obese. Glycemic control of diabetes was assessed measuring the levels of fasting blood glucose (FBG) and hemoglobin A_1c. A total of 14 patients had an eating disorder, and 7 of them had binge eating disorder (BED). The BED patients were combined with three bulimic patients and four patients with subclinical BED and classified as binge-eating related ED.

Although FBG and HbA_1c were significantly worse in patients with an eating disorder, compared with patients with normal eating patterns, the significance disappeared when body mass index (BMI) was added to the regression model. “Specifically, normal-BMI individuals exhibited a rate of ED of 8%, contrasted with a 26% prevalence of ED in obese patients,” the authors stated.

The findings were limited by the exploratory study design, small sample size, and lack of controlling for multiple variables, the researchers noted.

However, “although the objective negative clinical impact of an ED on type 2 diabetes control is yet to be confirmed, is possible to speculate that the remission of binge episodes could play a major role in diabetes treatment,” they said.

The researchers had no financial conflicts to disclose.
 

SOURCE: Papelbaum M et al. J Eat Disord. 2019 Sep 6. doi: 10.1186/s40337-019-0260-4.

Drizalma Sprinkle (duloxetine delayed-release capsule) has launched for the treatment of various neuropsychiatric and pain disorders in patients with difficulty swallowing, according to a release from Sun Pharma. It can be swallowed whole, sprinkled on applesauce, or administered via nasogastric tube.

Difficulty swallowing affects approximately 30%-35% of long-term care residents, but the main alternative – crushing tablets – introduces risks of its own to the administration process.

This sprinkle is indicated for the treatment of major depressive disorder in adults, generalized anxiety disorder in patients aged 7 years and older, diabetic peripheral neuropathic pain in adults, and chronic musculoskeletal pain in adults. It was approved by the Food and Drug Administration for these indications July 19, 2019.

It carries a boxed warning for suicidal thoughts and behaviors. The most common adverse reactions (5% or more of treated participants and twice the incidence with placebo) were nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis. The full prescribing information can be found on the FDA website.

cpalmer@mdedge.com

Drizalma Sprinkle (duloxetine delayed-release capsule) has launched for the treatment of various neuropsychiatric and pain disorders in patients with difficulty swallowing, according to a release from Sun Pharma. It can be swallowed whole, sprinkled on applesauce, or administered via nasogastric tube.

Difficulty swallowing affects approximately 30%-35% of long-term care residents, but the main alternative – crushing tablets – introduces risks of its own to the administration process.

This sprinkle is indicated for the treatment of major depressive disorder in adults, generalized anxiety disorder in patients aged 7 years and older, diabetic peripheral neuropathic pain in adults, and chronic musculoskeletal pain in adults. It was approved by the Food and Drug Administration for these indications July 19, 2019.

It carries a boxed warning for suicidal thoughts and behaviors. The most common adverse reactions (5% or more of treated participants and twice the incidence with placebo) were nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis. The full prescribing information can be found on the FDA website.

cpalmer@mdedge.com

Drizalma Sprinkle (duloxetine delayed-release capsule) has launched for the treatment of various neuropsychiatric and pain disorders in patients with difficulty swallowing, according to a release from Sun Pharma. It can be swallowed whole, sprinkled on applesauce, or administered via nasogastric tube.

Difficulty swallowing affects approximately 30%-35% of long-term care residents, but the main alternative – crushing tablets – introduces risks of its own to the administration process.

This sprinkle is indicated for the treatment of major depressive disorder in adults, generalized anxiety disorder in patients aged 7 years and older, diabetic peripheral neuropathic pain in adults, and chronic musculoskeletal pain in adults. It was approved by the Food and Drug Administration for these indications July 19, 2019.

It carries a boxed warning for suicidal thoughts and behaviors. The most common adverse reactions (5% or more of treated participants and twice the incidence with placebo) were nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis. The full prescribing information can be found on the FDA website.

cpalmer@mdedge.com

Symptoms of binge eating disorder can be assessed with a modified version of the Yale-Brown Obsessive Compulsive Scale, based on data from an analysis of three phase III studies.

The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) is designed to assess symptoms of binge eating disorder (BED), including binge eating thoughts and compulsiveness. “Psychometric testing and analysis of the Y-BOCS-BE is being conducted as a multistage process to optimize the characterization of BED,” wrote Karen Yee, PhD, of Shire (now part of Takeda), Boston, and colleagues.

In a study published in Quality of Life Research, investigators examined the validity of the Y-BOCS-BE in terms of dimensionality, internal consistency, convergent validity, test-retest reliability, and determination of clinically meaningful improvement. The Y-BOCS-BE is a 10-item clinician-rated scale with total scores from 0 to 4 on which 0 equals no symptoms and 4 equals extreme symptoms.

Overall, the Y-BOCS-BE’s internal consistency and convergent validity were maximized at 12 weeks, and test-retest reliability was maximized in an 8-week retest interval, minimal clinically important improvement could not be assessed in the two short-term efficacy studies, but “estimates in score reductions of 12-17 points were taken to represent the best estimates of clinically meaningful improvement,” the researchers said.

The findings were limited by several factors including the use of a study population of BED patients without psychiatric comorbidities, and the inclusion only of those who did not relapse the researchers noted. However, the results “set the stage for normalizing the Y-BOCS-BE and increasing the understanding of the clinical significance of Y-BOCS-BE scores and score changes to be useful both for clinical practice and clinical research,” they said.

Dr. Yee disclosed being employed by Shire and owning stock in Takeda. The studies were funded by Shire.

SOURCE: Yee K et al. Qual Life Res. 2019 Aug 31. doi: 10.1007/s11136-019-02277-8 .

Symptoms of binge eating disorder can be assessed with a modified version of the Yale-Brown Obsessive Compulsive Scale, based on data from an analysis of three phase III studies.

The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) is designed to assess symptoms of binge eating disorder (BED), including binge eating thoughts and compulsiveness. “Psychometric testing and analysis of the Y-BOCS-BE is being conducted as a multistage process to optimize the characterization of BED,” wrote Karen Yee, PhD, of Shire (now part of Takeda), Boston, and colleagues.

In a study published in Quality of Life Research, investigators examined the validity of the Y-BOCS-BE in terms of dimensionality, internal consistency, convergent validity, test-retest reliability, and determination of clinically meaningful improvement. The Y-BOCS-BE is a 10-item clinician-rated scale with total scores from 0 to 4 on which 0 equals no symptoms and 4 equals extreme symptoms.

Overall, the Y-BOCS-BE’s internal consistency and convergent validity were maximized at 12 weeks, and test-retest reliability was maximized in an 8-week retest interval, minimal clinically important improvement could not be assessed in the two short-term efficacy studies, but “estimates in score reductions of 12-17 points were taken to represent the best estimates of clinically meaningful improvement,” the researchers said.

The findings were limited by several factors including the use of a study population of BED patients without psychiatric comorbidities, and the inclusion only of those who did not relapse the researchers noted. However, the results “set the stage for normalizing the Y-BOCS-BE and increasing the understanding of the clinical significance of Y-BOCS-BE scores and score changes to be useful both for clinical practice and clinical research,” they said.

Dr. Yee disclosed being employed by Shire and owning stock in Takeda. The studies were funded by Shire.

SOURCE: Yee K et al. Qual Life Res. 2019 Aug 31. doi: 10.1007/s11136-019-02277-8 .

Symptoms of binge eating disorder can be assessed with a modified version of the Yale-Brown Obsessive Compulsive Scale, based on data from an analysis of three phase III studies.

The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) is designed to assess symptoms of binge eating disorder (BED), including binge eating thoughts and compulsiveness. “Psychometric testing and analysis of the Y-BOCS-BE is being conducted as a multistage process to optimize the characterization of BED,” wrote Karen Yee, PhD, of Shire (now part of Takeda), Boston, and colleagues.

In a study published in Quality of Life Research, investigators examined the validity of the Y-BOCS-BE in terms of dimensionality, internal consistency, convergent validity, test-retest reliability, and determination of clinically meaningful improvement. The Y-BOCS-BE is a 10-item clinician-rated scale with total scores from 0 to 4 on which 0 equals no symptoms and 4 equals extreme symptoms.

Overall, the Y-BOCS-BE’s internal consistency and convergent validity were maximized at 12 weeks, and test-retest reliability was maximized in an 8-week retest interval, minimal clinically important improvement could not be assessed in the two short-term efficacy studies, but “estimates in score reductions of 12-17 points were taken to represent the best estimates of clinically meaningful improvement,” the researchers said.

The findings were limited by several factors including the use of a study population of BED patients without psychiatric comorbidities, and the inclusion only of those who did not relapse the researchers noted. However, the results “set the stage for normalizing the Y-BOCS-BE and increasing the understanding of the clinical significance of Y-BOCS-BE scores and score changes to be useful both for clinical practice and clinical research,” they said.

Dr. Yee disclosed being employed by Shire and owning stock in Takeda. The studies were funded by Shire.

SOURCE: Yee K et al. Qual Life Res. 2019 Aug 31. doi: 10.1007/s11136-019-02277-8 .

Approximately half of college-aged women exhibit binge eating symptoms, and these women scored significantly higher on measures of depression, stress, and anxiety than do non–binge eaters, based on data from 154 women at a Palestine Polytechnic University in Hebron.

Previous studies show that binge eating disorder is multifactorial and associated with depression and anxiety, however, “To our knowledge, no study has yet assessed the prevalence of binge eating symptoms among female university students,” wrote Manal M. Badrasawi, PhD, of An-Najah National University, Tulkarm, Palestine, and colleagues.

In a cross-sectional study published in the Journal of Eating Disorders, the researchers interviewed 154 female college students in Palestine using the using BEDS-7 (Binge Eating Disorder Screener-7). The average age of the participants was 20 years.

Overall, 50% of the students showed positive binge eating symptoms, and these individuals had significantly higher scores on measures of depression, stress, and anxiety compared to individuals without binge eating symptoms.

Binge eating also was significantly associated with greater frequency of eating between meals and increased snacking, but no significant association was noted between binge eating and sociodemographic variables, including place of residence, marital status, and years of study. Binge eating was not significantly associated with weight status.

The researchers had no financial conflicts to disclose.

SOURCE: Badrasawi MM et al. J Eat Disord. 2019 Oct 2;7:33. doi: 10.1186/s40337-019-0263-1.2019.

Approximately half of college-aged women exhibit binge eating symptoms, and these women scored significantly higher on measures of depression, stress, and anxiety than do non–binge eaters, based on data from 154 women at a Palestine Polytechnic University in Hebron.

Previous studies show that binge eating disorder is multifactorial and associated with depression and anxiety, however, “To our knowledge, no study has yet assessed the prevalence of binge eating symptoms among female university students,” wrote Manal M. Badrasawi, PhD, of An-Najah National University, Tulkarm, Palestine, and colleagues.

In a cross-sectional study published in the Journal of Eating Disorders, the researchers interviewed 154 female college students in Palestine using the using BEDS-7 (Binge Eating Disorder Screener-7). The average age of the participants was 20 years.

Overall, 50% of the students showed positive binge eating symptoms, and these individuals had significantly higher scores on measures of depression, stress, and anxiety compared to individuals without binge eating symptoms.

Binge eating also was significantly associated with greater frequency of eating between meals and increased snacking, but no significant association was noted between binge eating and sociodemographic variables, including place of residence, marital status, and years of study. Binge eating was not significantly associated with weight status.

The researchers had no financial conflicts to disclose.

SOURCE: Badrasawi MM et al. J Eat Disord. 2019 Oct 2;7:33. doi: 10.1186/s40337-019-0263-1.2019.

Approximately half of college-aged women exhibit binge eating symptoms, and these women scored significantly higher on measures of depression, stress, and anxiety than do non–binge eaters, based on data from 154 women at a Palestine Polytechnic University in Hebron.

Previous studies show that binge eating disorder is multifactorial and associated with depression and anxiety, however, “To our knowledge, no study has yet assessed the prevalence of binge eating symptoms among female university students,” wrote Manal M. Badrasawi, PhD, of An-Najah National University, Tulkarm, Palestine, and colleagues.

In a cross-sectional study published in the Journal of Eating Disorders, the researchers interviewed 154 female college students in Palestine using the using BEDS-7 (Binge Eating Disorder Screener-7). The average age of the participants was 20 years.

Overall, 50% of the students showed positive binge eating symptoms, and these individuals had significantly higher scores on measures of depression, stress, and anxiety compared to individuals without binge eating symptoms.

Binge eating also was significantly associated with greater frequency of eating between meals and increased snacking, but no significant association was noted between binge eating and sociodemographic variables, including place of residence, marital status, and years of study. Binge eating was not significantly associated with weight status.

The researchers had no financial conflicts to disclose.

SOURCE: Badrasawi MM et al. J Eat Disord. 2019 Oct 2;7:33. doi: 10.1186/s40337-019-0263-1.2019.

WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.

copyright DesignPics/Thinkstock

One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.

In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.

These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.

“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.

The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.

Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.

The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.

mzoler@mdedge.com

SOURCE: ClinicalTrials.gov identifier: NCT02878330.

WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.

copyright DesignPics/Thinkstock

One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.

In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.

These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.

“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.

The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.

Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.

The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.

mzoler@mdedge.com

SOURCE: ClinicalTrials.gov identifier: NCT02878330.

WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.

copyright DesignPics/Thinkstock

One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.

In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.

These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.

“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.

The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.

Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.

The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.

mzoler@mdedge.com

SOURCE: ClinicalTrials.gov identifier: NCT02878330.

Despite improvement, more work needs to be done in the National Institutes of Health’s work in overseeing financial conflicts of interest in extramural research, the Department of Health & Human Services’ Office of Inspector General reported.

Kativ/iStockphoto

In highlighting the improvement in a September 2019 report, “NIH has made strides in reviewing financial conflicts of interest in extramural research, but could do more,” the OIG noted that, in the past 10 years, “NIH has strengthened its reporting requirements and developed an online system for collecting, reviewing, and storing financial conflicts of interest (FCOIs) that institutions report. These changes resulted in improvements in how NIH tracks and reviews FCOIs that institutions report.”

That being said, OIG also highlighted some ongoing issues with NIH’s FCOI oversight.

“Across the three NIH Institutes and Centers (ICs) that we reviewed, staff differed in the level of scrutiny they applied to their review of FCOIs,” the report states.

For example, the report notes that 15 of the 25 ICs have written procedures related to FCOI reviews and the documentation shared by the three ICs showed different levels of detail and instruction.

“Only one of the three guidance documents provided IC staff with specific criteria aimed at standardizing the review of FCOIs,” the report stated. Two of the three ICs also reported using external resources to aid in the review.

Review times also varied significantly, with two of the three ICs reporting that they spend generally 5-30 minutes per review, while the third said staff spends several hours on reviews.

The OIG also reported that “NIH lacks quality assurance procedures in its review process. Specifically, NIH central management and the three ICs that we reviewed do not perform any systematic analyses or even ad hoc checks to determine whether staff accurately and consistently review reported FCOIs, and OIG found a small number of inconsistencies in the FCOI data that institutions reported, which might highlight the need for more oversight of the review process.”

The report notes that there is a process in place to provide oversight of ICs’ review of reported FCOIs, but there is no longer sufficient staff to continue this oversight.

The “OER [Office of Extramural Research] now relies on IC staff to seek guidance when needed and does not conduct regular oversight of the ICs. Similarly, none of the three ICs we reviewed perform quality checks to ensure the thoroughness or consistency of review by program officials. Staff members from one IC stated that while they do not conduct quality checks, the IC provides new program officials more guidance during their first few reviews.”

The HHS watchdog also noted that NIH cannot identify whether FCOIs involve foreign entities even though investigators must disclose financial interests from foreign investments.

“The HHS regulations on FCOI do not require institutions to designate whether FCOIs involve foreign entities, and NIH reported that it has no plans to expand these regulations to include such a requirement,” the OIG reported.

The OIG recommended that NIH perform periodic quality assurance reviews of FCOI information to ensure adequacy of oversight and suggested it use “information regarding foreign affiliations and support that it collects during the pre-award process to decide whether to revise its FCOI review process to address concerns regarding foreign influence.”

gtwachtman@mdedge.com

SOURCE: Murrin S. Office of Inspector General. 2019 Sep 25. OEI-03-19-00150.

Despite improvement, more work needs to be done in the National Institutes of Health’s work in overseeing financial conflicts of interest in extramural research, the Department of Health & Human Services’ Office of Inspector General reported.

Kativ/iStockphoto

In highlighting the improvement in a September 2019 report, “NIH has made strides in reviewing financial conflicts of interest in extramural research, but could do more,” the OIG noted that, in the past 10 years, “NIH has strengthened its reporting requirements and developed an online system for collecting, reviewing, and storing financial conflicts of interest (FCOIs) that institutions report. These changes resulted in improvements in how NIH tracks and reviews FCOIs that institutions report.”

That being said, OIG also highlighted some ongoing issues with NIH’s FCOI oversight.

“Across the three NIH Institutes and Centers (ICs) that we reviewed, staff differed in the level of scrutiny they applied to their review of FCOIs,” the report states.

For example, the report notes that 15 of the 25 ICs have written procedures related to FCOI reviews and the documentation shared by the three ICs showed different levels of detail and instruction.

“Only one of the three guidance documents provided IC staff with specific criteria aimed at standardizing the review of FCOIs,” the report stated. Two of the three ICs also reported using external resources to aid in the review.

Review times also varied significantly, with two of the three ICs reporting that they spend generally 5-30 minutes per review, while the third said staff spends several hours on reviews.

The OIG also reported that “NIH lacks quality assurance procedures in its review process. Specifically, NIH central management and the three ICs that we reviewed do not perform any systematic analyses or even ad hoc checks to determine whether staff accurately and consistently review reported FCOIs, and OIG found a small number of inconsistencies in the FCOI data that institutions reported, which might highlight the need for more oversight of the review process.”

The report notes that there is a process in place to provide oversight of ICs’ review of reported FCOIs, but there is no longer sufficient staff to continue this oversight.

The “OER [Office of Extramural Research] now relies on IC staff to seek guidance when needed and does not conduct regular oversight of the ICs. Similarly, none of the three ICs we reviewed perform quality checks to ensure the thoroughness or consistency of review by program officials. Staff members from one IC stated that while they do not conduct quality checks, the IC provides new program officials more guidance during their first few reviews.”

The HHS watchdog also noted that NIH cannot identify whether FCOIs involve foreign entities even though investigators must disclose financial interests from foreign investments.

“The HHS regulations on FCOI do not require institutions to designate whether FCOIs involve foreign entities, and NIH reported that it has no plans to expand these regulations to include such a requirement,” the OIG reported.

The OIG recommended that NIH perform periodic quality assurance reviews of FCOI information to ensure adequacy of oversight and suggested it use “information regarding foreign affiliations and support that it collects during the pre-award process to decide whether to revise its FCOI review process to address concerns regarding foreign influence.”

gtwachtman@mdedge.com

SOURCE: Murrin S. Office of Inspector General. 2019 Sep 25. OEI-03-19-00150.

Despite improvement, more work needs to be done in the National Institutes of Health’s work in overseeing financial conflicts of interest in extramural research, the Department of Health & Human Services’ Office of Inspector General reported.

Kativ/iStockphoto

In highlighting the improvement in a September 2019 report, “NIH has made strides in reviewing financial conflicts of interest in extramural research, but could do more,” the OIG noted that, in the past 10 years, “NIH has strengthened its reporting requirements and developed an online system for collecting, reviewing, and storing financial conflicts of interest (FCOIs) that institutions report. These changes resulted in improvements in how NIH tracks and reviews FCOIs that institutions report.”

That being said, OIG also highlighted some ongoing issues with NIH’s FCOI oversight.

“Across the three NIH Institutes and Centers (ICs) that we reviewed, staff differed in the level of scrutiny they applied to their review of FCOIs,” the report states.

For example, the report notes that 15 of the 25 ICs have written procedures related to FCOI reviews and the documentation shared by the three ICs showed different levels of detail and instruction.

“Only one of the three guidance documents provided IC staff with specific criteria aimed at standardizing the review of FCOIs,” the report stated. Two of the three ICs also reported using external resources to aid in the review.

Review times also varied significantly, with two of the three ICs reporting that they spend generally 5-30 minutes per review, while the third said staff spends several hours on reviews.

The OIG also reported that “NIH lacks quality assurance procedures in its review process. Specifically, NIH central management and the three ICs that we reviewed do not perform any systematic analyses or even ad hoc checks to determine whether staff accurately and consistently review reported FCOIs, and OIG found a small number of inconsistencies in the FCOI data that institutions reported, which might highlight the need for more oversight of the review process.”

The report notes that there is a process in place to provide oversight of ICs’ review of reported FCOIs, but there is no longer sufficient staff to continue this oversight.

The “OER [Office of Extramural Research] now relies on IC staff to seek guidance when needed and does not conduct regular oversight of the ICs. Similarly, none of the three ICs we reviewed perform quality checks to ensure the thoroughness or consistency of review by program officials. Staff members from one IC stated that while they do not conduct quality checks, the IC provides new program officials more guidance during their first few reviews.”

The HHS watchdog also noted that NIH cannot identify whether FCOIs involve foreign entities even though investigators must disclose financial interests from foreign investments.

“The HHS regulations on FCOI do not require institutions to designate whether FCOIs involve foreign entities, and NIH reported that it has no plans to expand these regulations to include such a requirement,” the OIG reported.

The OIG recommended that NIH perform periodic quality assurance reviews of FCOI information to ensure adequacy of oversight and suggested it use “information regarding foreign affiliations and support that it collects during the pre-award process to decide whether to revise its FCOI review process to address concerns regarding foreign influence.”

gtwachtman@mdedge.com

SOURCE: Murrin S. Office of Inspector General. 2019 Sep 25. OEI-03-19-00150.

Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.

My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.

I have always been curious about frequent genetic disease carrier states, and like any overachiever, keen to explain my own deficiencies away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”

Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).

Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).

Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.

This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.

My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.

I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*

Oh boy. I had to go sit in my office, turn out the lights, and cry.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.

Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.

My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.

I have always been curious about frequent genetic disease carrier states, and like any overachiever, keen to explain my own deficiencies away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”

Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).

Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).

Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.

This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.

My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.

I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*

Oh boy. I had to go sit in my office, turn out the lights, and cry.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.

Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.

My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.

I have always been curious about frequent genetic disease carrier states, and like any overachiever, keen to explain my own deficiencies away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”

Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).

Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).

Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.

This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.

My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.

I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*

Oh boy. I had to go sit in my office, turn out the lights, and cry.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at dermnews@mdedge.com.

* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.

AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.

“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.

In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)

The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.

Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.

The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).

The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).

No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.

Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.

A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.

Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
 

SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.

AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.

“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.

In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)

The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.

Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.

The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).

The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).

No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.

Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.

A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.

Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
 

SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.

AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.

“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.

In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)

The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.

Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.

The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).

The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).

No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.

Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.

A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.

Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
 

SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.

AUSTIN, TEX. – Patients with Charcot-Marie-Tooth disease (CMT) receive a range of supportive care that includes physical therapy, surgery, medications, orthoses, and walking aids, according to patient-reported data presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. Patients describe approaches to CMT management that are broadly consistent with guidelines, researchers said.

“The range of different CMT treatments was wide,” reported Tjalf Ziemssen, MD, PhD, a researcher at Technische Universität Dresden in Germany, and colleagues. “Of note, high proportions of respondents had received pain medication, and a relatively high number had also visited pain specialists. These results indicate that pain may have a substantial impact on people with CMT.”

The data also suggest that “lower-limb problems and mobility issues have a considerable impact on people with CMT,” they said.

CMT is a rare, progressive neuropathy that leads to distal muscle weakness, muscle atrophy, and sensory loss. There is no cure, and patients rely on supportive care. Until recently, few studies have assessed the impact of CMT on patients’ lives.

An ongoing, international, 2-year observational study is collecting data from adults with CMT. Patients report data via an app called CMT & Me.

To examine patient-reported treatment patterns and care standards for CMT in the United States and the United Kingdom, Dr. Ziemssen and colleagues analyzed data through Aug. 5, 2019, about 9.5 months into the study. Their interim analysis included data from 439 patients, including 222 patients in the United Kingdom and 217 in the United States.

More than 70% of participants visit a family doctor each year, and a similar proportion visit a neurologist. About 40% visit physical therapists, orthotists, or podiatrists. Other health care professionals seen by patients include occupational therapists (20%), orthopedic surgeons (nearly 20%), and pain specialists (about 15%).

About 70% of participants had received rehabilitation therapy such as physical therapy or occupational therapy, and about 70% had used medications, most frequently nonopioid analgesics (about 50%) and antidepressants (about 30%).

More than 80% used orthoses or walking aids, most commonly ankle or leg braces, insoles, or walking sticks.

In addition, about half of respondents had undergone a surgery for CMT. The most common procedures were osteotomy, hammertoe correction, and plantar fascia release.

Together, patients saw about a dozen types of health care professionals. “Small proportions of participants had visited each professional, which suggests that the care requirements of CMT patients are varied,” the researchers said.

The study was sponsored by Pharnext. Dr. Ziemssen and coauthors received compensation for participating in the study. Other coauthors are employees of Pharnext or Vitaccess, the company that developed the app used in the study.

jremaly@mdedge.com

SOURCE: Ziemssen T et al. AANEM 2019. Abstract 83. Treatment of Charcot-Marie-Tooth Disease in the United Kingdom and United States.

AUSTIN, TEX. – Patients with Charcot-Marie-Tooth disease (CMT) receive a range of supportive care that includes physical therapy, surgery, medications, orthoses, and walking aids, according to patient-reported data presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. Patients describe approaches to CMT management that are broadly consistent with guidelines, researchers said.

“The range of different CMT treatments was wide,” reported Tjalf Ziemssen, MD, PhD, a researcher at Technische Universität Dresden in Germany, and colleagues. “Of note, high proportions of respondents had received pain medication, and a relatively high number had also visited pain specialists. These results indicate that pain may have a substantial impact on people with CMT.”

The data also suggest that “lower-limb problems and mobility issues have a considerable impact on people with CMT,” they said.

CMT is a rare, progressive neuropathy that leads to distal muscle weakness, muscle atrophy, and sensory loss. There is no cure, and patients rely on supportive care. Until recently, few studies have assessed the impact of CMT on patients’ lives.

An ongoing, international, 2-year observational study is collecting data from adults with CMT. Patients report data via an app called CMT & Me.

To examine patient-reported treatment patterns and care standards for CMT in the United States and the United Kingdom, Dr. Ziemssen and colleagues analyzed data through Aug. 5, 2019, about 9.5 months into the study. Their interim analysis included data from 439 patients, including 222 patients in the United Kingdom and 217 in the United States.

More than 70% of participants visit a family doctor each year, and a similar proportion visit a neurologist. About 40% visit physical therapists, orthotists, or podiatrists. Other health care professionals seen by patients include occupational therapists (20%), orthopedic surgeons (nearly 20%), and pain specialists (about 15%).

About 70% of participants had received rehabilitation therapy such as physical therapy or occupational therapy, and about 70% had used medications, most frequently nonopioid analgesics (about 50%) and antidepressants (about 30%).

More than 80% used orthoses or walking aids, most commonly ankle or leg braces, insoles, or walking sticks.

In addition, about half of respondents had undergone a surgery for CMT. The most common procedures were osteotomy, hammertoe correction, and plantar fascia release.

Together, patients saw about a dozen types of health care professionals. “Small proportions of participants had visited each professional, which suggests that the care requirements of CMT patients are varied,” the researchers said.

The study was sponsored by Pharnext. Dr. Ziemssen and coauthors received compensation for participating in the study. Other coauthors are employees of Pharnext or Vitaccess, the company that developed the app used in the study.

jremaly@mdedge.com

SOURCE: Ziemssen T et al. AANEM 2019. Abstract 83. Treatment of Charcot-Marie-Tooth Disease in the United Kingdom and United States.

AUSTIN, TEX. – Patients with Charcot-Marie-Tooth disease (CMT) receive a range of supportive care that includes physical therapy, surgery, medications, orthoses, and walking aids, according to patient-reported data presented at the annual meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine. Patients describe approaches to CMT management that are broadly consistent with guidelines, researchers said.

“The range of different CMT treatments was wide,” reported Tjalf Ziemssen, MD, PhD, a researcher at Technische Universität Dresden in Germany, and colleagues. “Of note, high proportions of respondents had received pain medication, and a relatively high number had also visited pain specialists. These results indicate that pain may have a substantial impact on people with CMT.”

The data also suggest that “lower-limb problems and mobility issues have a considerable impact on people with CMT,” they said.

CMT is a rare, progressive neuropathy that leads to distal muscle weakness, muscle atrophy, and sensory loss. There is no cure, and patients rely on supportive care. Until recently, few studies have assessed the impact of CMT on patients’ lives.

An ongoing, international, 2-year observational study is collecting data from adults with CMT. Patients report data via an app called CMT & Me.

To examine patient-reported treatment patterns and care standards for CMT in the United States and the United Kingdom, Dr. Ziemssen and colleagues analyzed data through Aug. 5, 2019, about 9.5 months into the study. Their interim analysis included data from 439 patients, including 222 patients in the United Kingdom and 217 in the United States.

More than 70% of participants visit a family doctor each year, and a similar proportion visit a neurologist. About 40% visit physical therapists, orthotists, or podiatrists. Other health care professionals seen by patients include occupational therapists (20%), orthopedic surgeons (nearly 20%), and pain specialists (about 15%).

About 70% of participants had received rehabilitation therapy such as physical therapy or occupational therapy, and about 70% had used medications, most frequently nonopioid analgesics (about 50%) and antidepressants (about 30%).

More than 80% used orthoses or walking aids, most commonly ankle or leg braces, insoles, or walking sticks.

In addition, about half of respondents had undergone a surgery for CMT. The most common procedures were osteotomy, hammertoe correction, and plantar fascia release.

Together, patients saw about a dozen types of health care professionals. “Small proportions of participants had visited each professional, which suggests that the care requirements of CMT patients are varied,” the researchers said.

The study was sponsored by Pharnext. Dr. Ziemssen and coauthors received compensation for participating in the study. Other coauthors are employees of Pharnext or Vitaccess, the company that developed the app used in the study.

jremaly@mdedge.com

SOURCE: Ziemssen T et al. AANEM 2019. Abstract 83. Treatment of Charcot-Marie-Tooth Disease in the United Kingdom and United States.