Heidi Splete

Aclidinium bromide reduced exacerbations in adults with chronic obstructive pulmonary disease with no increased risk of major adverse cardiovascular events, compared with placebo, in a randomized trial of more than 3,000 patients.

Aclidinium, a long-acting muscarinic antagonist (LAMA), has been shown to reduce COPD exacerbation in the short term, but long-term effectiveness has not been examined, wrote Robert A. Wise, MD, of Johns Hopkins University, Baltimore, and colleagues.

ASCENT-COPD is a multicenter, double-blind, randomized, placebo-controlled, parallel-group noninferiority study conducted at 522 sites in the United States and Canada. A paper on recent data from ASCENT-COPD, published in JAMA, supports early findings reported last year at the American Thoracic Society meeting.

The researchers randomized adults with COPD to a 400-mg dose of aclidinium bromide twice daily, or placebo. The average age of the patients was 67 years; 59% were men. The median exposure time to aclidinium or placebo was 365 days during the first year of treatment, and the median exposure overall was 495 days for aclidinium patients and 478 days for placebo patients.

Of the 2,537 patients who completed the study, 69 (3.9%) in the aclidinium group and 76 (4.2%) in the placebo group experienced a major adverse cardiovascular event (MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke).

In addition, annual rates of moderate to severe COPD exacerbations were significantly lower in the aclidinium patients compared with placebo patients (0.44 vs. 0.57, P less than .001).

In a secondary analysis with a definition of MACE expanded to include heart failure, arrhythmias, or cerebrovascular disease, results remained similar between the groups; events occurred in 168 aclidinium patients (9.4%) and 160 placebo patients (8.9%). The rate of COPD exacerbations requiring hospitalization was significantly lower in aclidinium patients, compared with placebo patients (0.07 vs. 0.10, P = .006).

Overall, the most common treatment-emergent adverse events were similar in the aclidinium and placebo groups, respectively; pneumonia (6.1% vs. 5.8%), urinary tract infections (5.2% vs. 5.0%), and upper respiratory tract infections (4.8% vs. 5.6%). The most common serious adverse events (in at least 1% of patients) were pneumonia, atrial fibrillation, heart failure, and coronary artery disease. Dry mouth and urinary retention were rare, and occurred in less than 1% of patients in each group.

“No patient subgroup demonstrated a difference in efficacy except when analyzed by baseline COPD severity, in which the treatment benefit was observed only in patients with FEV₁ [forced expiratory volume in 1 second] of 50% predicted or less,” the researchers noted. “This may be explained by the lower exacerbation rate seen in the placebo group in patients with moderate airway obstruction vs. severe or very severe obstruction,” they said.

“Outcomes of this trial add data to the long-standing controversy over the safety of LAMAs in COPD” and support the need for additional research, they said.

The study findings were limited by several factors including insufficient power to detect cause-specific mortality and the use of a LAMA with low risk of systemic effects, the researchers noted.

SOURCE: Wise R et al. JAMA. 2019. 321:1693-1701.

Aclidinium bromide reduced exacerbations in adults with chronic obstructive pulmonary disease with no increased risk of major adverse cardiovascular events, compared with placebo, in a randomized trial of more than 3,000 patients.

Aclidinium, a long-acting muscarinic antagonist (LAMA), has been shown to reduce COPD exacerbation in the short term, but long-term effectiveness has not been examined, wrote Robert A. Wise, MD, of Johns Hopkins University, Baltimore, and colleagues.

ASCENT-COPD is a multicenter, double-blind, randomized, placebo-controlled, parallel-group noninferiority study conducted at 522 sites in the United States and Canada. A paper on recent data from ASCENT-COPD, published in JAMA, supports early findings reported last year at the American Thoracic Society meeting.

The researchers randomized adults with COPD to a 400-mg dose of aclidinium bromide twice daily, or placebo. The average age of the patients was 67 years; 59% were men. The median exposure time to aclidinium or placebo was 365 days during the first year of treatment, and the median exposure overall was 495 days for aclidinium patients and 478 days for placebo patients.

Of the 2,537 patients who completed the study, 69 (3.9%) in the aclidinium group and 76 (4.2%) in the placebo group experienced a major adverse cardiovascular event (MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke).

In addition, annual rates of moderate to severe COPD exacerbations were significantly lower in the aclidinium patients compared with placebo patients (0.44 vs. 0.57, P less than .001).

In a secondary analysis with a definition of MACE expanded to include heart failure, arrhythmias, or cerebrovascular disease, results remained similar between the groups; events occurred in 168 aclidinium patients (9.4%) and 160 placebo patients (8.9%). The rate of COPD exacerbations requiring hospitalization was significantly lower in aclidinium patients, compared with placebo patients (0.07 vs. 0.10, P = .006).

Overall, the most common treatment-emergent adverse events were similar in the aclidinium and placebo groups, respectively; pneumonia (6.1% vs. 5.8%), urinary tract infections (5.2% vs. 5.0%), and upper respiratory tract infections (4.8% vs. 5.6%). The most common serious adverse events (in at least 1% of patients) were pneumonia, atrial fibrillation, heart failure, and coronary artery disease. Dry mouth and urinary retention were rare, and occurred in less than 1% of patients in each group.

“No patient subgroup demonstrated a difference in efficacy except when analyzed by baseline COPD severity, in which the treatment benefit was observed only in patients with FEV₁ [forced expiratory volume in 1 second] of 50% predicted or less,” the researchers noted. “This may be explained by the lower exacerbation rate seen in the placebo group in patients with moderate airway obstruction vs. severe or very severe obstruction,” they said.

“Outcomes of this trial add data to the long-standing controversy over the safety of LAMAs in COPD” and support the need for additional research, they said.

The study findings were limited by several factors including insufficient power to detect cause-specific mortality and the use of a LAMA with low risk of systemic effects, the researchers noted.

SOURCE: Wise R et al. JAMA. 2019. 321:1693-1701.

Aclidinium bromide reduced exacerbations in adults with chronic obstructive pulmonary disease with no increased risk of major adverse cardiovascular events, compared with placebo, in a randomized trial of more than 3,000 patients.

Aclidinium, a long-acting muscarinic antagonist (LAMA), has been shown to reduce COPD exacerbation in the short term, but long-term effectiveness has not been examined, wrote Robert A. Wise, MD, of Johns Hopkins University, Baltimore, and colleagues.

ASCENT-COPD is a multicenter, double-blind, randomized, placebo-controlled, parallel-group noninferiority study conducted at 522 sites in the United States and Canada. A paper on recent data from ASCENT-COPD, published in JAMA, supports early findings reported last year at the American Thoracic Society meeting.

The researchers randomized adults with COPD to a 400-mg dose of aclidinium bromide twice daily, or placebo. The average age of the patients was 67 years; 59% were men. The median exposure time to aclidinium or placebo was 365 days during the first year of treatment, and the median exposure overall was 495 days for aclidinium patients and 478 days for placebo patients.

Of the 2,537 patients who completed the study, 69 (3.9%) in the aclidinium group and 76 (4.2%) in the placebo group experienced a major adverse cardiovascular event (MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke).

In addition, annual rates of moderate to severe COPD exacerbations were significantly lower in the aclidinium patients compared with placebo patients (0.44 vs. 0.57, P less than .001).

In a secondary analysis with a definition of MACE expanded to include heart failure, arrhythmias, or cerebrovascular disease, results remained similar between the groups; events occurred in 168 aclidinium patients (9.4%) and 160 placebo patients (8.9%). The rate of COPD exacerbations requiring hospitalization was significantly lower in aclidinium patients, compared with placebo patients (0.07 vs. 0.10, P = .006).

Overall, the most common treatment-emergent adverse events were similar in the aclidinium and placebo groups, respectively; pneumonia (6.1% vs. 5.8%), urinary tract infections (5.2% vs. 5.0%), and upper respiratory tract infections (4.8% vs. 5.6%). The most common serious adverse events (in at least 1% of patients) were pneumonia, atrial fibrillation, heart failure, and coronary artery disease. Dry mouth and urinary retention were rare, and occurred in less than 1% of patients in each group.

“No patient subgroup demonstrated a difference in efficacy except when analyzed by baseline COPD severity, in which the treatment benefit was observed only in patients with FEV₁ [forced expiratory volume in 1 second] of 50% predicted or less,” the researchers noted. “This may be explained by the lower exacerbation rate seen in the placebo group in patients with moderate airway obstruction vs. severe or very severe obstruction,” they said.

“Outcomes of this trial add data to the long-standing controversy over the safety of LAMAs in COPD” and support the need for additional research, they said.

The study findings were limited by several factors including insufficient power to detect cause-specific mortality and the use of a LAMA with low risk of systemic effects, the researchers noted.

SOURCE: Wise R et al. JAMA. 2019. 321:1693-1701.

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.

KatarzynaBialasiewicz/Thinkstock

Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.

To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).

Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.

Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.

The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.

“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.

The investigators are employed by Pfizer, which funded the study.

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.

The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.

KatarzynaBialasiewicz/Thinkstock

Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.

To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).

Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.

Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.

The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.

“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.

The investigators are employed by Pfizer, which funded the study.

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.

The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.

KatarzynaBialasiewicz/Thinkstock

Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.

To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).

Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.

Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.

The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.

“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.

The investigators are employed by Pfizer, which funded the study.

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.

A single oral dose of aspirin did not improve the sensitivity of the fecal immunochemical test to identify advanced colorectal neoplasms in a randomized trial of 2,134 adults.

The study was inspired by an observational study in which the sensitivity of the fecal immunochemical test (FIT) was enhanced in adults taking aspirin for cardiovascular disease prevention.

It was surmised that “aspirin predisposes to subclinical bleeding and, hence, increased detection of advanced adenomas by FIT. This suggests that administration of aspirin prior to fecal sampling might be a practical intervention to increase FIT sensitivity,” wrote Hermann Brenner, MD, of the German Cancer Research Center, Heidelberg, and colleagues.

In a study published in JAMA, the researchers analyzed 2,134 adults aged 40-80 years who were scheduled for colonoscopy. The study participants, who had no recent use of aspirin or other drugs with antithrombotic effects, were randomized to a 300-mg aspirin tablet or a placebo tablet 2 days before stool samples were obtained. The average age of the participants was 60 years, and 78% of the colonoscopies were for primary screening.

Overall, 224 of the study participants had advanced neoplasms, including 216 individuals with advanced adenoma and 8 with colorectal cancer.

Sensitivity was not significantly different between the aspirin and placebo groups at either of two predefined cutoffs of 10.2-mcg Hb/g stool (40.2% and 30.4%, respectively) and 17-mcg Hb/g stool (28.6% and 22.5%, respectively).

Two serious adverse events occurred in the aspirin group but were not considered related to aspirin. No serious adverse events were reported in the placebo group.

Although the results do not support the findings from previous observational studies, they suggest the need for more research of the potential impact of aspirin on FIT sensitivity, the researchers said.

“This trial was designed to detect a 24% absolute increase in sensitivity and was not adequately powered to detect small differences that may nevertheless be clinically meaningful given the low morbidity observed, the low cost of a single dose of aspirin, and the ease of implementation of this intervention across health systems,” they explained.

Additional limitations of the study included lack of adjustment for multiple testing in secondary analyses, inability to analyze subtypes of advanced neoplasms, and the inclusion of only one round of screening. FIT programs usually include multiple rounds, the researchers said. Therefore, “potential effects on detection of advanced neoplasms and reduction of CRC incidence and mortality in the long run are yet to be determined.”

SOURCE: Brenner H et al. JAMA. 2019;321(17):1686-1692.

A single oral dose of aspirin did not improve the sensitivity of the fecal immunochemical test to identify advanced colorectal neoplasms in a randomized trial of 2,134 adults.

The study was inspired by an observational study in which the sensitivity of the fecal immunochemical test (FIT) was enhanced in adults taking aspirin for cardiovascular disease prevention.

It was surmised that “aspirin predisposes to subclinical bleeding and, hence, increased detection of advanced adenomas by FIT. This suggests that administration of aspirin prior to fecal sampling might be a practical intervention to increase FIT sensitivity,” wrote Hermann Brenner, MD, of the German Cancer Research Center, Heidelberg, and colleagues.

In a study published in JAMA, the researchers analyzed 2,134 adults aged 40-80 years who were scheduled for colonoscopy. The study participants, who had no recent use of aspirin or other drugs with antithrombotic effects, were randomized to a 300-mg aspirin tablet or a placebo tablet 2 days before stool samples were obtained. The average age of the participants was 60 years, and 78% of the colonoscopies were for primary screening.

Overall, 224 of the study participants had advanced neoplasms, including 216 individuals with advanced adenoma and 8 with colorectal cancer.

Sensitivity was not significantly different between the aspirin and placebo groups at either of two predefined cutoffs of 10.2-mcg Hb/g stool (40.2% and 30.4%, respectively) and 17-mcg Hb/g stool (28.6% and 22.5%, respectively).

Two serious adverse events occurred in the aspirin group but were not considered related to aspirin. No serious adverse events were reported in the placebo group.

Although the results do not support the findings from previous observational studies, they suggest the need for more research of the potential impact of aspirin on FIT sensitivity, the researchers said.

“This trial was designed to detect a 24% absolute increase in sensitivity and was not adequately powered to detect small differences that may nevertheless be clinically meaningful given the low morbidity observed, the low cost of a single dose of aspirin, and the ease of implementation of this intervention across health systems,” they explained.

Additional limitations of the study included lack of adjustment for multiple testing in secondary analyses, inability to analyze subtypes of advanced neoplasms, and the inclusion of only one round of screening. FIT programs usually include multiple rounds, the researchers said. Therefore, “potential effects on detection of advanced neoplasms and reduction of CRC incidence and mortality in the long run are yet to be determined.”

SOURCE: Brenner H et al. JAMA. 2019;321(17):1686-1692.

A single oral dose of aspirin did not improve the sensitivity of the fecal immunochemical test to identify advanced colorectal neoplasms in a randomized trial of 2,134 adults.

The study was inspired by an observational study in which the sensitivity of the fecal immunochemical test (FIT) was enhanced in adults taking aspirin for cardiovascular disease prevention.

It was surmised that “aspirin predisposes to subclinical bleeding and, hence, increased detection of advanced adenomas by FIT. This suggests that administration of aspirin prior to fecal sampling might be a practical intervention to increase FIT sensitivity,” wrote Hermann Brenner, MD, of the German Cancer Research Center, Heidelberg, and colleagues.

In a study published in JAMA, the researchers analyzed 2,134 adults aged 40-80 years who were scheduled for colonoscopy. The study participants, who had no recent use of aspirin or other drugs with antithrombotic effects, were randomized to a 300-mg aspirin tablet or a placebo tablet 2 days before stool samples were obtained. The average age of the participants was 60 years, and 78% of the colonoscopies were for primary screening.

Overall, 224 of the study participants had advanced neoplasms, including 216 individuals with advanced adenoma and 8 with colorectal cancer.

Sensitivity was not significantly different between the aspirin and placebo groups at either of two predefined cutoffs of 10.2-mcg Hb/g stool (40.2% and 30.4%, respectively) and 17-mcg Hb/g stool (28.6% and 22.5%, respectively).

Two serious adverse events occurred in the aspirin group but were not considered related to aspirin. No serious adverse events were reported in the placebo group.

Although the results do not support the findings from previous observational studies, they suggest the need for more research of the potential impact of aspirin on FIT sensitivity, the researchers said.

“This trial was designed to detect a 24% absolute increase in sensitivity and was not adequately powered to detect small differences that may nevertheless be clinically meaningful given the low morbidity observed, the low cost of a single dose of aspirin, and the ease of implementation of this intervention across health systems,” they explained.

Additional limitations of the study included lack of adjustment for multiple testing in secondary analyses, inability to analyze subtypes of advanced neoplasms, and the inclusion of only one round of screening. FIT programs usually include multiple rounds, the researchers said. Therefore, “potential effects on detection of advanced neoplasms and reduction of CRC incidence and mortality in the long run are yet to be determined.”

SOURCE: Brenner H et al. JAMA. 2019;321(17):1686-1692.

Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary. 

“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).

To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.

Overall, sexual assault was significantly more likely for transgender teens with restroom and locker room restrictions at school compared to those without such restrictions, with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.

The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.

Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.

The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.

“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.

The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.

However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.

“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.

The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.

SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .

Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary. 

“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).

To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.

Overall, sexual assault was significantly more likely for transgender teens with restroom and locker room restrictions at school compared to those without such restrictions, with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.

The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.

Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.

The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.

“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.

The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.

However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.

“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.

The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.

SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .

Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary. 

“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).

To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.

Overall, sexual assault was significantly more likely for transgender teens with restroom and locker room restrictions at school compared to those without such restrictions, with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.

The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.

Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.

The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.

“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.

The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.

However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.

“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.

The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.

SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .

Suicides and calls to the National Suicide Prevention Lifeline spiked after the suicide of actor Robin Williams, based on data from calls and website visits before and after his death.

John J. Kruzel/ Wikimedia Commons

Suicides in the United States tend to follow temporal patterns, with spikes in the spring and early summer, but “some events, including celebrity deaths, serve as ‘shocks’ that disrupt seasonal time trends and may prompt imitation,” wrote Rajeev Ramchand, PhD, of the National Institute of Mental Health, Bethesda, Md., and colleagues in a study published online in the journal Psychiatric Services in Advance (2019 Apr 30. doi: 10.1176/appi.ps.201900007).

The National Suicide Prevention Lifeline (NSPL) experienced a 300% increase in call volume the day after Mr. Williams’ death, however, only 57% of these calls were answered, the researchers said.

The researchers compared daily suicide data, NSPL call volume, and visits to two suicide prevention websites before and after Mr. Williams’ death on August 11, 2014.

Before August 11 in 2012, 2013, and 2014, the average number of daily suicides ranged from 113 to 117; after August 11, 2014, this average spiked to 142, an increase not seen in 2012 or 2013, according to data from the National Center for Health Statistics’ Compressed Mortality File. The NSPL received 12,972 calls on August 12, 2014, following Mr. Williams’ death, compared with a daily average of 4,116 to 6,302 calls during the week before his death. In addition, the Suicide Prevention Resource Center (SPRC), a website that provides technical assistance, training, and suicide prevention material; and Suicide Awareness Voices of Education (SAVE), a website with resources for individuals affected by suicide, as well educational information to raise public awareness, saw significant increases in visits on the day after Mr. Williams’ suicide.

The study findings were limited by several factors including the lack of information on whether calls to NSPL were information seekers or individuals in crisis, the researchers noted. However, the results suggest the need for surge capacity to prepare for increased demand in the wake of a celebrity suicide, they said.

The researchers had no financial conflicts to disclose.

SOURCE: Ramchand R et al. Psychiatric Services in Advance. 2019. doi: 10.1176/appi.ps.201900007 .

Suicides and calls to the National Suicide Prevention Lifeline spiked after the suicide of actor Robin Williams, based on data from calls and website visits before and after his death.

John J. Kruzel/ Wikimedia Commons

Suicides in the United States tend to follow temporal patterns, with spikes in the spring and early summer, but “some events, including celebrity deaths, serve as ‘shocks’ that disrupt seasonal time trends and may prompt imitation,” wrote Rajeev Ramchand, PhD, of the National Institute of Mental Health, Bethesda, Md., and colleagues in a study published online in the journal Psychiatric Services in Advance (2019 Apr 30. doi: 10.1176/appi.ps.201900007).

The National Suicide Prevention Lifeline (NSPL) experienced a 300% increase in call volume the day after Mr. Williams’ death, however, only 57% of these calls were answered, the researchers said.

The researchers compared daily suicide data, NSPL call volume, and visits to two suicide prevention websites before and after Mr. Williams’ death on August 11, 2014.

Before August 11 in 2012, 2013, and 2014, the average number of daily suicides ranged from 113 to 117; after August 11, 2014, this average spiked to 142, an increase not seen in 2012 or 2013, according to data from the National Center for Health Statistics’ Compressed Mortality File. The NSPL received 12,972 calls on August 12, 2014, following Mr. Williams’ death, compared with a daily average of 4,116 to 6,302 calls during the week before his death. In addition, the Suicide Prevention Resource Center (SPRC), a website that provides technical assistance, training, and suicide prevention material; and Suicide Awareness Voices of Education (SAVE), a website with resources for individuals affected by suicide, as well educational information to raise public awareness, saw significant increases in visits on the day after Mr. Williams’ suicide.

The study findings were limited by several factors including the lack of information on whether calls to NSPL were information seekers or individuals in crisis, the researchers noted. However, the results suggest the need for surge capacity to prepare for increased demand in the wake of a celebrity suicide, they said.

The researchers had no financial conflicts to disclose.

SOURCE: Ramchand R et al. Psychiatric Services in Advance. 2019. doi: 10.1176/appi.ps.201900007 .

Suicides and calls to the National Suicide Prevention Lifeline spiked after the suicide of actor Robin Williams, based on data from calls and website visits before and after his death.

John J. Kruzel/ Wikimedia Commons

Suicides in the United States tend to follow temporal patterns, with spikes in the spring and early summer, but “some events, including celebrity deaths, serve as ‘shocks’ that disrupt seasonal time trends and may prompt imitation,” wrote Rajeev Ramchand, PhD, of the National Institute of Mental Health, Bethesda, Md., and colleagues in a study published online in the journal Psychiatric Services in Advance (2019 Apr 30. doi: 10.1176/appi.ps.201900007).

The National Suicide Prevention Lifeline (NSPL) experienced a 300% increase in call volume the day after Mr. Williams’ death, however, only 57% of these calls were answered, the researchers said.

The researchers compared daily suicide data, NSPL call volume, and visits to two suicide prevention websites before and after Mr. Williams’ death on August 11, 2014.

Before August 11 in 2012, 2013, and 2014, the average number of daily suicides ranged from 113 to 117; after August 11, 2014, this average spiked to 142, an increase not seen in 2012 or 2013, according to data from the National Center for Health Statistics’ Compressed Mortality File. The NSPL received 12,972 calls on August 12, 2014, following Mr. Williams’ death, compared with a daily average of 4,116 to 6,302 calls during the week before his death. In addition, the Suicide Prevention Resource Center (SPRC), a website that provides technical assistance, training, and suicide prevention material; and Suicide Awareness Voices of Education (SAVE), a website with resources for individuals affected by suicide, as well educational information to raise public awareness, saw significant increases in visits on the day after Mr. Williams’ suicide.

The study findings were limited by several factors including the lack of information on whether calls to NSPL were information seekers or individuals in crisis, the researchers noted. However, the results suggest the need for surge capacity to prepare for increased demand in the wake of a celebrity suicide, they said.

The researchers had no financial conflicts to disclose.

SOURCE: Ramchand R et al. Psychiatric Services in Advance. 2019. doi: 10.1176/appi.ps.201900007 .

Alirocumab has received an updated indication from the Food and Drug Administration for reducing the overall risk of major adverse cardiovascular events in patients with a recent acute coronary event.

Alirocumab is designed to inhibit the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to LDL receptors, thereby lowering LDL cholesterol, according to manufacturer Regeneron, which is developing alirocumab in partnership with Sanofi.  

The drug was previously approved in the United States as an adjunct treatment along with diet and maximally tolerated statin therapy to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.

The approval of the supplemental Biologics License Application was supported by data from the ODYSSEY Outcomes trial in which 18,924 patients who had an acute coronary syndrome were randomized to alirocumab or placebo plus background high-intensity statin therapy starting at a median of 2.6 months after the event. Over 3 years’ follow-up, a composite endpoint outcome including death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina occurred in 9.5% of alirocumab patients and 11.1% of placebo patients.

In the study, patients received subcutaneous dose of 75 mg of alirocumab every 2 weeks, which was adjusted to achieve an LDL cholesterol level of 25-50 mg/dL. The most significant benefits occurred among patients with a baseline LDL cholesterol of 100 mg/dL or higher who were taking high-intensity statins, which supports the role of LDL cholesterol reduction in improving outcomes for coronary syndrome patients, according to study investigators.

Alirocumab is given as a subcutaneous injection. The most common side effects include pain and tenderness at the injection site, and redness, itching, or swelling; some patients have reported symptoms of a common cold or flu.

More details of the ODYSSEY Outcomes trial were presented at the annual meeting of the American College of Cardiology.
 

Alirocumab has received an updated indication from the Food and Drug Administration for reducing the overall risk of major adverse cardiovascular events in patients with a recent acute coronary event.

Alirocumab is designed to inhibit the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to LDL receptors, thereby lowering LDL cholesterol, according to manufacturer Regeneron, which is developing alirocumab in partnership with Sanofi.  

The drug was previously approved in the United States as an adjunct treatment along with diet and maximally tolerated statin therapy to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.

The approval of the supplemental Biologics License Application was supported by data from the ODYSSEY Outcomes trial in which 18,924 patients who had an acute coronary syndrome were randomized to alirocumab or placebo plus background high-intensity statin therapy starting at a median of 2.6 months after the event. Over 3 years’ follow-up, a composite endpoint outcome including death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina occurred in 9.5% of alirocumab patients and 11.1% of placebo patients.

In the study, patients received subcutaneous dose of 75 mg of alirocumab every 2 weeks, which was adjusted to achieve an LDL cholesterol level of 25-50 mg/dL. The most significant benefits occurred among patients with a baseline LDL cholesterol of 100 mg/dL or higher who were taking high-intensity statins, which supports the role of LDL cholesterol reduction in improving outcomes for coronary syndrome patients, according to study investigators.

Alirocumab is given as a subcutaneous injection. The most common side effects include pain and tenderness at the injection site, and redness, itching, or swelling; some patients have reported symptoms of a common cold or flu.

More details of the ODYSSEY Outcomes trial were presented at the annual meeting of the American College of Cardiology.
 

Alirocumab has received an updated indication from the Food and Drug Administration for reducing the overall risk of major adverse cardiovascular events in patients with a recent acute coronary event.

Alirocumab is designed to inhibit the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to LDL receptors, thereby lowering LDL cholesterol, according to manufacturer Regeneron, which is developing alirocumab in partnership with Sanofi.  

The drug was previously approved in the United States as an adjunct treatment along with diet and maximally tolerated statin therapy to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.

The approval of the supplemental Biologics License Application was supported by data from the ODYSSEY Outcomes trial in which 18,924 patients who had an acute coronary syndrome were randomized to alirocumab or placebo plus background high-intensity statin therapy starting at a median of 2.6 months after the event. Over 3 years’ follow-up, a composite endpoint outcome including death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina occurred in 9.5% of alirocumab patients and 11.1% of placebo patients.

In the study, patients received subcutaneous dose of 75 mg of alirocumab every 2 weeks, which was adjusted to achieve an LDL cholesterol level of 25-50 mg/dL. The most significant benefits occurred among patients with a baseline LDL cholesterol of 100 mg/dL or higher who were taking high-intensity statins, which supports the role of LDL cholesterol reduction in improving outcomes for coronary syndrome patients, according to study investigators.

Alirocumab is given as a subcutaneous injection. The most common side effects include pain and tenderness at the injection site, and redness, itching, or swelling; some patients have reported symptoms of a common cold or flu.

More details of the ODYSSEY Outcomes trial were presented at the annual meeting of the American College of Cardiology.
 

Risankizumab, an interleukin-23 inhibitor, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the manufacturer announced on April 23.

Risankizumab selectively inhibits interleukin-23 (IL-23), a key inflammatory protein, by binding to its p19 subunit. The drug is administered at a dose of 150 mg, in two subcutaneous injections, every 12 weeks, after starting doses at weeks 0 and 4. It will be available in early May, according to an AbbVie press release announcing the approval.

The approval was based in part on data from two phase 3, 2-year studies, In UltIMMA-1 and UltIMMA-2, at 16 weeks, 75% of risankizumab patients in both studies achieved a Psoriasis Area and Severity Index (PASI 90), compared with 5% and 2% of those on placebo, respectively. These results were published in 2018 (Lancet. 2018 Aug 25;392[10148]:650-61).

At 1 year, 82% and 81% of those treated with risankizumab in the two studies achieved a PASI 90, and 56% and 60% achieved a PASI 100, respectively, according to the company.

Approval was also based on additional phase 3 studies, IMMhance and IMMvent.

Upper respiratory infections were among the most common adverse events associated with risankizumab in trials, reported in 13%, according to the company. Other adverse events associated with treatment included headache (3.5 %), fatigue (2.5 %), injection site reactions (1.5%) and tinea infections (1.1%). The AbbVie release states that candidates for treatment should be evaluated for tuberculosis before starting therapy, and patients should be instructed to report signs and symptoms of infection.

Risankizumab, which will be marketed as Skyrizi, was recently approved in Canada for the same indication, and in Japan, for plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adults. It currently is under review in Europe.

AbbVie and Boehringer Ingelheim are collaborating on the development of risankizumab, according to an AbbVie press release. Studies of risankizumab for treatment of psoriatic arthritis and Crohn’s disease are underway.

Risankizumab, an interleukin-23 inhibitor, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the manufacturer announced on April 23.

Risankizumab selectively inhibits interleukin-23 (IL-23), a key inflammatory protein, by binding to its p19 subunit. The drug is administered at a dose of 150 mg, in two subcutaneous injections, every 12 weeks, after starting doses at weeks 0 and 4. It will be available in early May, according to an AbbVie press release announcing the approval.

The approval was based in part on data from two phase 3, 2-year studies, In UltIMMA-1 and UltIMMA-2, at 16 weeks, 75% of risankizumab patients in both studies achieved a Psoriasis Area and Severity Index (PASI 90), compared with 5% and 2% of those on placebo, respectively. These results were published in 2018 (Lancet. 2018 Aug 25;392[10148]:650-61).

At 1 year, 82% and 81% of those treated with risankizumab in the two studies achieved a PASI 90, and 56% and 60% achieved a PASI 100, respectively, according to the company.

Approval was also based on additional phase 3 studies, IMMhance and IMMvent.

Upper respiratory infections were among the most common adverse events associated with risankizumab in trials, reported in 13%, according to the company. Other adverse events associated with treatment included headache (3.5 %), fatigue (2.5 %), injection site reactions (1.5%) and tinea infections (1.1%). The AbbVie release states that candidates for treatment should be evaluated for tuberculosis before starting therapy, and patients should be instructed to report signs and symptoms of infection.

Risankizumab, which will be marketed as Skyrizi, was recently approved in Canada for the same indication, and in Japan, for plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adults. It currently is under review in Europe.

AbbVie and Boehringer Ingelheim are collaborating on the development of risankizumab, according to an AbbVie press release. Studies of risankizumab for treatment of psoriatic arthritis and Crohn’s disease are underway.

Risankizumab, an interleukin-23 inhibitor, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the manufacturer announced on April 23.

Risankizumab selectively inhibits interleukin-23 (IL-23), a key inflammatory protein, by binding to its p19 subunit. The drug is administered at a dose of 150 mg, in two subcutaneous injections, every 12 weeks, after starting doses at weeks 0 and 4. It will be available in early May, according to an AbbVie press release announcing the approval.

The approval was based in part on data from two phase 3, 2-year studies, In UltIMMA-1 and UltIMMA-2, at 16 weeks, 75% of risankizumab patients in both studies achieved a Psoriasis Area and Severity Index (PASI 90), compared with 5% and 2% of those on placebo, respectively. These results were published in 2018 (Lancet. 2018 Aug 25;392[10148]:650-61).

At 1 year, 82% and 81% of those treated with risankizumab in the two studies achieved a PASI 90, and 56% and 60% achieved a PASI 100, respectively, according to the company.

Approval was also based on additional phase 3 studies, IMMhance and IMMvent.

Upper respiratory infections were among the most common adverse events associated with risankizumab in trials, reported in 13%, according to the company. Other adverse events associated with treatment included headache (3.5 %), fatigue (2.5 %), injection site reactions (1.5%) and tinea infections (1.1%). The AbbVie release states that candidates for treatment should be evaluated for tuberculosis before starting therapy, and patients should be instructed to report signs and symptoms of infection.

Risankizumab, which will be marketed as Skyrizi, was recently approved in Canada for the same indication, and in Japan, for plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adults. It currently is under review in Europe.

AbbVie and Boehringer Ingelheim are collaborating on the development of risankizumab, according to an AbbVie press release. Studies of risankizumab for treatment of psoriatic arthritis and Crohn’s disease are underway.

New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.

The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.

The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”

The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.

The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.

The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.

The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.

“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.

“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.

The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.

Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.

SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.

New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.

The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.

The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”

The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.

The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.

The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.

The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.

“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.

“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.

The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.

Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.

SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.

New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.

The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.

The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”

The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.

The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.

The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.

The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.

“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.

“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.

The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.

Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.

SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.

A continuously updating database of clinical and genomic details on patients with non–small cell lung cancer accurately represented correlations between genomics and outcomes, based on an analysis of more than 4,000 patients.

“Most efforts to identify clinicogenomic associations currently rely on clinical trials, single-institution series, or national registries,” wrote Gaurav Singal, MD, of Foundation Medicine in Cambridge, Mass., and colleagues in JAMA.

To explore the feasibility of a clinicogenomic database, the researchers combined clinical data from electronic health records with comprehensive genetic profiling data from 28,889 patients; 4,064 adults with non–small cell lung cancer were included in the analysis of associations among tumor genomics, patient characteristics, and clinical outcomes. The data were collected between Jan. 1, 2011, and Jan. 1, 2018, from 275 U.S. oncology practices.

The researchers examined implications of clinical and genomic features for 3,522 patients with advanced disease. Among these, the median overall survival was 10.3 months and the 5-year survival rate was 3.8%. Factors influencing a longer overall survival included never smoking and having nonsquamous pathology; the presence of mutations in genes TP53 and RB1 were associated with shorter survival.

For each patient, researchers calculated the tumor mutational burden (TMB), defined as “a measure of the number of somatic mutations identified per megabase of DNA sequenced.” TMB was significantly higher among smokers, compared with nonsmokers, and “alterations in EGFR, ALK, ROS1, and RET were associated with significantly lower TMB than wild-type cases,” the researchers wrote.

Overall, the results “replicated previously described associations between clinical and genomic characteristics, driver mutations and response to targeted therapy, and TMB and response to immunotherapy,” the researchers wrote.

The findings were limited by several factors, notably the quality and completeness of mortality data, as well as potential biases from the inclusion of comprehensive genetic profiling results and analysis of therapeutic exposures in an unrandomized trial, as well as a study population limited to patients with advanced stage disease, the researchers noted.

However, the results support data from similar studies and further show that clinicogenomic databases can be used in research to augment drug development and improve the design of clinical trials, they wrote.

The study was supported by Flatiron Health and Foundation Medicine, which are both owned by the Roche Group. Dr. Singal and several coauthors are employees of Foundation Medicine.

SOURCE: Singal G et al. JAMA. 2019;321:1391-9.

A continuously updating database of clinical and genomic details on patients with non–small cell lung cancer accurately represented correlations between genomics and outcomes, based on an analysis of more than 4,000 patients.

“Most efforts to identify clinicogenomic associations currently rely on clinical trials, single-institution series, or national registries,” wrote Gaurav Singal, MD, of Foundation Medicine in Cambridge, Mass., and colleagues in JAMA.

To explore the feasibility of a clinicogenomic database, the researchers combined clinical data from electronic health records with comprehensive genetic profiling data from 28,889 patients; 4,064 adults with non–small cell lung cancer were included in the analysis of associations among tumor genomics, patient characteristics, and clinical outcomes. The data were collected between Jan. 1, 2011, and Jan. 1, 2018, from 275 U.S. oncology practices.

The researchers examined implications of clinical and genomic features for 3,522 patients with advanced disease. Among these, the median overall survival was 10.3 months and the 5-year survival rate was 3.8%. Factors influencing a longer overall survival included never smoking and having nonsquamous pathology; the presence of mutations in genes TP53 and RB1 were associated with shorter survival.

For each patient, researchers calculated the tumor mutational burden (TMB), defined as “a measure of the number of somatic mutations identified per megabase of DNA sequenced.” TMB was significantly higher among smokers, compared with nonsmokers, and “alterations in EGFR, ALK, ROS1, and RET were associated with significantly lower TMB than wild-type cases,” the researchers wrote.

Overall, the results “replicated previously described associations between clinical and genomic characteristics, driver mutations and response to targeted therapy, and TMB and response to immunotherapy,” the researchers wrote.

The findings were limited by several factors, notably the quality and completeness of mortality data, as well as potential biases from the inclusion of comprehensive genetic profiling results and analysis of therapeutic exposures in an unrandomized trial, as well as a study population limited to patients with advanced stage disease, the researchers noted.

However, the results support data from similar studies and further show that clinicogenomic databases can be used in research to augment drug development and improve the design of clinical trials, they wrote.

The study was supported by Flatiron Health and Foundation Medicine, which are both owned by the Roche Group. Dr. Singal and several coauthors are employees of Foundation Medicine.

SOURCE: Singal G et al. JAMA. 2019;321:1391-9.

A continuously updating database of clinical and genomic details on patients with non–small cell lung cancer accurately represented correlations between genomics and outcomes, based on an analysis of more than 4,000 patients.

“Most efforts to identify clinicogenomic associations currently rely on clinical trials, single-institution series, or national registries,” wrote Gaurav Singal, MD, of Foundation Medicine in Cambridge, Mass., and colleagues in JAMA.

To explore the feasibility of a clinicogenomic database, the researchers combined clinical data from electronic health records with comprehensive genetic profiling data from 28,889 patients; 4,064 adults with non–small cell lung cancer were included in the analysis of associations among tumor genomics, patient characteristics, and clinical outcomes. The data were collected between Jan. 1, 2011, and Jan. 1, 2018, from 275 U.S. oncology practices.

The researchers examined implications of clinical and genomic features for 3,522 patients with advanced disease. Among these, the median overall survival was 10.3 months and the 5-year survival rate was 3.8%. Factors influencing a longer overall survival included never smoking and having nonsquamous pathology; the presence of mutations in genes TP53 and RB1 were associated with shorter survival.

For each patient, researchers calculated the tumor mutational burden (TMB), defined as “a measure of the number of somatic mutations identified per megabase of DNA sequenced.” TMB was significantly higher among smokers, compared with nonsmokers, and “alterations in EGFR, ALK, ROS1, and RET were associated with significantly lower TMB than wild-type cases,” the researchers wrote.

Overall, the results “replicated previously described associations between clinical and genomic characteristics, driver mutations and response to targeted therapy, and TMB and response to immunotherapy,” the researchers wrote.

The findings were limited by several factors, notably the quality and completeness of mortality data, as well as potential biases from the inclusion of comprehensive genetic profiling results and analysis of therapeutic exposures in an unrandomized trial, as well as a study population limited to patients with advanced stage disease, the researchers noted.

However, the results support data from similar studies and further show that clinicogenomic databases can be used in research to augment drug development and improve the design of clinical trials, they wrote.

The study was supported by Flatiron Health and Foundation Medicine, which are both owned by the Roche Group. Dr. Singal and several coauthors are employees of Foundation Medicine.

SOURCE: Singal G et al. JAMA. 2019;321:1391-9.