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Christopher Palmer has been an associate editor at MDedge News since 2017. When he's not tidying grammar, he writes short pieces about breaking FDA announcements and approvals, as well as journal articles. He proudly holds a BA in English and philosophy. Follow him on Twitter @cmacmpalm.
Firdapse approved: First treatment for rare autoimmune disorder
The Food and Drug Administration has approved amifampridine (Firdapse) as the first treatment for the rare autoimmune disorder known as Lambert-Eaton myasthenic syndrome, which causes the immune system to attack the neuromuscular junction and thereby disrupts the nerves’ ability to send signals to muscle cells. This causes fatigue and weakness in those affected, so they can experience difficulties with activities of daily living as a result.
The most common side effects included prickling sensation, upper respiratory tract infection, abdominal pain, and muscle spasms.
More information can be found in the FDA’s press announcement.
The Food and Drug Administration has approved amifampridine (Firdapse) as the first treatment for the rare autoimmune disorder known as Lambert-Eaton myasthenic syndrome, which causes the immune system to attack the neuromuscular junction and thereby disrupts the nerves’ ability to send signals to muscle cells. This causes fatigue and weakness in those affected, so they can experience difficulties with activities of daily living as a result.
The most common side effects included prickling sensation, upper respiratory tract infection, abdominal pain, and muscle spasms.
More information can be found in the FDA’s press announcement.
The Food and Drug Administration has approved amifampridine (Firdapse) as the first treatment for the rare autoimmune disorder known as Lambert-Eaton myasthenic syndrome, which causes the immune system to attack the neuromuscular junction and thereby disrupts the nerves’ ability to send signals to muscle cells. This causes fatigue and weakness in those affected, so they can experience difficulties with activities of daily living as a result.
The most common side effects included prickling sensation, upper respiratory tract infection, abdominal pain, and muscle spasms.
More information can be found in the FDA’s press announcement.
Temixys plus other antiretrovirals approved for HIV-1
The Food and Drug Administration has approved the combination of lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) known as Temixys for treatment of HIV-1 when used with other antiretrovirals. The approval is for adult and pediatric patients with HIV-1 who weigh at least 35 kg.
The approval is based on data through 144 weeks in a double-blind, active-controlled, multicenter trial in 600 antiretroviral-naive patients. The trial compared TDF/3TC plus efavirenz (EFV) with 3TC/EFV plus stavudine (d4T). The results showed similar responses at 144 weeks between both groups: 62% of patients taking TDF/3TC/EFV and 58% of patients taking d4T/3TC/EFV achieved and maintained fewer than 50 copies/mL of HIV-1 RNA.
The most common adverse events include headache, pain, depression, rash, and diarrhea. Prior to initiating treatment, patients should be tested for hepatitis B virus because there have been reports of 3TC-resistant strains of hepatitis B virus associated with treatment of HIV-1 with 3TC-containing regimens in coinfected patients. Patients should also be tested for estimated creatinine clearance, urine glucose, and urine protein because TDF/3TC is not recommended for patients with renal impairment.
The full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved the combination of lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) known as Temixys for treatment of HIV-1 when used with other antiretrovirals. The approval is for adult and pediatric patients with HIV-1 who weigh at least 35 kg.
The approval is based on data through 144 weeks in a double-blind, active-controlled, multicenter trial in 600 antiretroviral-naive patients. The trial compared TDF/3TC plus efavirenz (EFV) with 3TC/EFV plus stavudine (d4T). The results showed similar responses at 144 weeks between both groups: 62% of patients taking TDF/3TC/EFV and 58% of patients taking d4T/3TC/EFV achieved and maintained fewer than 50 copies/mL of HIV-1 RNA.
The most common adverse events include headache, pain, depression, rash, and diarrhea. Prior to initiating treatment, patients should be tested for hepatitis B virus because there have been reports of 3TC-resistant strains of hepatitis B virus associated with treatment of HIV-1 with 3TC-containing regimens in coinfected patients. Patients should also be tested for estimated creatinine clearance, urine glucose, and urine protein because TDF/3TC is not recommended for patients with renal impairment.
The full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved the combination of lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) known as Temixys for treatment of HIV-1 when used with other antiretrovirals. The approval is for adult and pediatric patients with HIV-1 who weigh at least 35 kg.
The approval is based on data through 144 weeks in a double-blind, active-controlled, multicenter trial in 600 antiretroviral-naive patients. The trial compared TDF/3TC plus efavirenz (EFV) with 3TC/EFV plus stavudine (d4T). The results showed similar responses at 144 weeks between both groups: 62% of patients taking TDF/3TC/EFV and 58% of patients taking d4T/3TC/EFV achieved and maintained fewer than 50 copies/mL of HIV-1 RNA.
The most common adverse events include headache, pain, depression, rash, and diarrhea. Prior to initiating treatment, patients should be tested for hepatitis B virus because there have been reports of 3TC-resistant strains of hepatitis B virus associated with treatment of HIV-1 with 3TC-containing regimens in coinfected patients. Patients should also be tested for estimated creatinine clearance, urine glucose, and urine protein because TDF/3TC is not recommended for patients with renal impairment.
The full prescribing information can be found on the FDA website.
Comorbid depression, anxiety linked to doubled risk of diabetes
Comorbid symptoms of anxiety and depression are associated with twice the risk of developing type 2 diabetes, according to a research paper published in the Journal of Affective Disorders.
The researchers sampled 78,025 Dutch adults aged 30-75 years from the Lifelines Cohort Study and assessed them for depressive and anxious symptoms using the Mini-International Neuropsychiatric Interview before sorting them into groups based on whether they had both, depressive symptoms alone, anxious symptoms alone, or neither.
reported Sonya S. Deschênes, PhD, of the department of psychiatry at McGill University, Montreal, and her associates. Furthermore, in an analysis that adjusted for sociodemographic and lifestyle factors and a family history of diabetes, Dr. Deschênes and her associates found that the participants with both kinds of symptoms had an OR of 1.93 (95% CI, 1.21-3.07) of developing type 2 diabetes. Those with only depressive or anxious symptoms alone did not have a statistically significant risk of developing type 2 diabetes.
A limitation cited by the researchers is that a screening tool was used to assess depressive and anxiety symptoms. Also, glycosylated hemoglobin data were available only for a subset of the participants.
Nevertheless, Dr. Deschênes and her associates wrote, the “study extends ... prior findings and suggests that having co-occurring symptoms of [depression] and anxiety is most strongly associated with an increased risk of [type 2 diabetes]. This study also provides further support for the notion that depression with comorbid anxiety symptoms might represent a group with distinct features.”
SOURCE: Deschênes SS et al. J Affect Disorder. 2018 Oct 1. doi: 10.1016/j.jad.2018.05.029.
Comorbid symptoms of anxiety and depression are associated with twice the risk of developing type 2 diabetes, according to a research paper published in the Journal of Affective Disorders.
The researchers sampled 78,025 Dutch adults aged 30-75 years from the Lifelines Cohort Study and assessed them for depressive and anxious symptoms using the Mini-International Neuropsychiatric Interview before sorting them into groups based on whether they had both, depressive symptoms alone, anxious symptoms alone, or neither.
reported Sonya S. Deschênes, PhD, of the department of psychiatry at McGill University, Montreal, and her associates. Furthermore, in an analysis that adjusted for sociodemographic and lifestyle factors and a family history of diabetes, Dr. Deschênes and her associates found that the participants with both kinds of symptoms had an OR of 1.93 (95% CI, 1.21-3.07) of developing type 2 diabetes. Those with only depressive or anxious symptoms alone did not have a statistically significant risk of developing type 2 diabetes.
A limitation cited by the researchers is that a screening tool was used to assess depressive and anxiety symptoms. Also, glycosylated hemoglobin data were available only for a subset of the participants.
Nevertheless, Dr. Deschênes and her associates wrote, the “study extends ... prior findings and suggests that having co-occurring symptoms of [depression] and anxiety is most strongly associated with an increased risk of [type 2 diabetes]. This study also provides further support for the notion that depression with comorbid anxiety symptoms might represent a group with distinct features.”
SOURCE: Deschênes SS et al. J Affect Disorder. 2018 Oct 1. doi: 10.1016/j.jad.2018.05.029.
Comorbid symptoms of anxiety and depression are associated with twice the risk of developing type 2 diabetes, according to a research paper published in the Journal of Affective Disorders.
The researchers sampled 78,025 Dutch adults aged 30-75 years from the Lifelines Cohort Study and assessed them for depressive and anxious symptoms using the Mini-International Neuropsychiatric Interview before sorting them into groups based on whether they had both, depressive symptoms alone, anxious symptoms alone, or neither.
reported Sonya S. Deschênes, PhD, of the department of psychiatry at McGill University, Montreal, and her associates. Furthermore, in an analysis that adjusted for sociodemographic and lifestyle factors and a family history of diabetes, Dr. Deschênes and her associates found that the participants with both kinds of symptoms had an OR of 1.93 (95% CI, 1.21-3.07) of developing type 2 diabetes. Those with only depressive or anxious symptoms alone did not have a statistically significant risk of developing type 2 diabetes.
A limitation cited by the researchers is that a screening tool was used to assess depressive and anxiety symptoms. Also, glycosylated hemoglobin data were available only for a subset of the participants.
Nevertheless, Dr. Deschênes and her associates wrote, the “study extends ... prior findings and suggests that having co-occurring symptoms of [depression] and anxiety is most strongly associated with an increased risk of [type 2 diabetes]. This study also provides further support for the notion that depression with comorbid anxiety symptoms might represent a group with distinct features.”
SOURCE: Deschênes SS et al. J Affect Disorder. 2018 Oct 1. doi: 10.1016/j.jad.2018.05.029.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Some statins worse than others for musculoskeletal adverse event onset time
The FDA Adverse Event Reporting System database Quarterly Data Files (Q1 2004 to Q3 2017) published by the FDA (downloaded in February 2018) was used to evaluate the adverse events associated with statin therapy. Among the seven statins looked at in this study, atorvastatin and rosuvastatin contributed to both the most cases of musculoskeletal adverse events and also to some of the shortest times to onset; atorvastatin was associated with 454 cases and a median time to onset of 24.5 days, and rosuvastatin was associated with 413 cases and a median time to onset of 30 days. Simvastatin also contributed to a large number of cases (409), but the median time to onset was significantly faster with the other two statins according to a Steel-Dwass test.
The study also looked at whether and how much concomitant use of nonstatin drugs affected time to onset, but it found that none of the drugs evaluated in the study had an effect on time to onset.
Read more about this study in Pharmacology Research & Perspectives.
The FDA Adverse Event Reporting System database Quarterly Data Files (Q1 2004 to Q3 2017) published by the FDA (downloaded in February 2018) was used to evaluate the adverse events associated with statin therapy. Among the seven statins looked at in this study, atorvastatin and rosuvastatin contributed to both the most cases of musculoskeletal adverse events and also to some of the shortest times to onset; atorvastatin was associated with 454 cases and a median time to onset of 24.5 days, and rosuvastatin was associated with 413 cases and a median time to onset of 30 days. Simvastatin also contributed to a large number of cases (409), but the median time to onset was significantly faster with the other two statins according to a Steel-Dwass test.
The study also looked at whether and how much concomitant use of nonstatin drugs affected time to onset, but it found that none of the drugs evaluated in the study had an effect on time to onset.
Read more about this study in Pharmacology Research & Perspectives.
The FDA Adverse Event Reporting System database Quarterly Data Files (Q1 2004 to Q3 2017) published by the FDA (downloaded in February 2018) was used to evaluate the adverse events associated with statin therapy. Among the seven statins looked at in this study, atorvastatin and rosuvastatin contributed to both the most cases of musculoskeletal adverse events and also to some of the shortest times to onset; atorvastatin was associated with 454 cases and a median time to onset of 24.5 days, and rosuvastatin was associated with 413 cases and a median time to onset of 30 days. Simvastatin also contributed to a large number of cases (409), but the median time to onset was significantly faster with the other two statins according to a Steel-Dwass test.
The study also looked at whether and how much concomitant use of nonstatin drugs affected time to onset, but it found that none of the drugs evaluated in the study had an effect on time to onset.
Read more about this study in Pharmacology Research & Perspectives.
FROM PHARMACOLOGY RESEARCH & PERSPECTIVES
Physical activity tied to lower depression risk among older adults
Meeting World Health Organization recommendations for levels of physical activity reduces the odds of prevalent depression by 40%, according to a study of more than 4,000 adults aged 50 years and older.
“To [our] knowledge, this is the first prospective cohort study to examine the protective effect of meeting [moderate to vigorous physical activity] guidelines, and different volumes of walking, on depression among a sample of adults,” Cillian P. McDowell, of the University of Limerick (Ireland), and his associates wrote in Experimental Gerontology.
The study drew on data from The Irish Longitudinal Study of Ageing and included 4,556 individuals, 56.7% of whom were female. The investigators created “dose categories” based on how much exercise participants performed each week. For moderate to vigorous physical activity, they assigned participants to low (0 to less than 600 metabolic equivalent [MET]–minutes per week), moderate (600 to less than 1,200 MET-min/week), and high (1,200 or more MET-min/week) categories. For walking, investigators divided participants among tertiles of minutes performed (0-110 min/week, 120-400 min/week, and 420 or more min/week). Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression Scale, reported Mr. McDowell and his associates.
The odds of prevalent depression were 40% lower (odds ratio, 0.60; 95% confidence interval, 0.48-0.76) among participants who met the physical activity guidelines, 23% lower (OR, 0.77, 95% confidence interval, 0.49-1.21) among those who were in the moderate and high categories, and 43% lower (OR, 0.57; 95% CI, 0.45-0.73) among those who were in the moderate and high categories, Mr. McDowell and his associates wrote.
The study was not conducted to explore possible mechanisms underlying the ties between physical activity and depression. However, Mr. McDowell and his associates speculated that exercise training has both brain monoaminergic and neurotropic effects and might lower “inflammatory and oxidant markers. Further, physical activity may be associated with depression through psychological factors such as self-esteem.”
Mr. McDowell and his associates wrote. “Recent evidence has shown that people with [major depressive disorder] engage in higher levels of sedentary behavior, and that cross-sectionally sedentary behavior, is positively associated with depression,” they added. “Meeting WHO recommended [physical activity] levels could be recommended ... to prevent the onset of depression.”
The investigators pointed out that one of the major limitations of the study was that participants’ depression and activity were self-reported, which could predispose results to over- or underreporting. They also pointed out that a strength of the study was its large sample size.
Mr. McDowell and his associates reported no conflicts of interest. The sponsors of The Irish Longitudinal Study of Ageing played no role in this study’s design, methods, subject recruitment, data collection, analysis, or preparation.
SOURCE: McDowell CP et al. Exp Gerontol. 2018 Oct 2;112:68-75.
Meeting World Health Organization recommendations for levels of physical activity reduces the odds of prevalent depression by 40%, according to a study of more than 4,000 adults aged 50 years and older.
“To [our] knowledge, this is the first prospective cohort study to examine the protective effect of meeting [moderate to vigorous physical activity] guidelines, and different volumes of walking, on depression among a sample of adults,” Cillian P. McDowell, of the University of Limerick (Ireland), and his associates wrote in Experimental Gerontology.
The study drew on data from The Irish Longitudinal Study of Ageing and included 4,556 individuals, 56.7% of whom were female. The investigators created “dose categories” based on how much exercise participants performed each week. For moderate to vigorous physical activity, they assigned participants to low (0 to less than 600 metabolic equivalent [MET]–minutes per week), moderate (600 to less than 1,200 MET-min/week), and high (1,200 or more MET-min/week) categories. For walking, investigators divided participants among tertiles of minutes performed (0-110 min/week, 120-400 min/week, and 420 or more min/week). Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression Scale, reported Mr. McDowell and his associates.
The odds of prevalent depression were 40% lower (odds ratio, 0.60; 95% confidence interval, 0.48-0.76) among participants who met the physical activity guidelines, 23% lower (OR, 0.77, 95% confidence interval, 0.49-1.21) among those who were in the moderate and high categories, and 43% lower (OR, 0.57; 95% CI, 0.45-0.73) among those who were in the moderate and high categories, Mr. McDowell and his associates wrote.
The study was not conducted to explore possible mechanisms underlying the ties between physical activity and depression. However, Mr. McDowell and his associates speculated that exercise training has both brain monoaminergic and neurotropic effects and might lower “inflammatory and oxidant markers. Further, physical activity may be associated with depression through psychological factors such as self-esteem.”
Mr. McDowell and his associates wrote. “Recent evidence has shown that people with [major depressive disorder] engage in higher levels of sedentary behavior, and that cross-sectionally sedentary behavior, is positively associated with depression,” they added. “Meeting WHO recommended [physical activity] levels could be recommended ... to prevent the onset of depression.”
The investigators pointed out that one of the major limitations of the study was that participants’ depression and activity were self-reported, which could predispose results to over- or underreporting. They also pointed out that a strength of the study was its large sample size.
Mr. McDowell and his associates reported no conflicts of interest. The sponsors of The Irish Longitudinal Study of Ageing played no role in this study’s design, methods, subject recruitment, data collection, analysis, or preparation.
SOURCE: McDowell CP et al. Exp Gerontol. 2018 Oct 2;112:68-75.
Meeting World Health Organization recommendations for levels of physical activity reduces the odds of prevalent depression by 40%, according to a study of more than 4,000 adults aged 50 years and older.
“To [our] knowledge, this is the first prospective cohort study to examine the protective effect of meeting [moderate to vigorous physical activity] guidelines, and different volumes of walking, on depression among a sample of adults,” Cillian P. McDowell, of the University of Limerick (Ireland), and his associates wrote in Experimental Gerontology.
The study drew on data from The Irish Longitudinal Study of Ageing and included 4,556 individuals, 56.7% of whom were female. The investigators created “dose categories” based on how much exercise participants performed each week. For moderate to vigorous physical activity, they assigned participants to low (0 to less than 600 metabolic equivalent [MET]–minutes per week), moderate (600 to less than 1,200 MET-min/week), and high (1,200 or more MET-min/week) categories. For walking, investigators divided participants among tertiles of minutes performed (0-110 min/week, 120-400 min/week, and 420 or more min/week). Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression Scale, reported Mr. McDowell and his associates.
The odds of prevalent depression were 40% lower (odds ratio, 0.60; 95% confidence interval, 0.48-0.76) among participants who met the physical activity guidelines, 23% lower (OR, 0.77, 95% confidence interval, 0.49-1.21) among those who were in the moderate and high categories, and 43% lower (OR, 0.57; 95% CI, 0.45-0.73) among those who were in the moderate and high categories, Mr. McDowell and his associates wrote.
The study was not conducted to explore possible mechanisms underlying the ties between physical activity and depression. However, Mr. McDowell and his associates speculated that exercise training has both brain monoaminergic and neurotropic effects and might lower “inflammatory and oxidant markers. Further, physical activity may be associated with depression through psychological factors such as self-esteem.”
Mr. McDowell and his associates wrote. “Recent evidence has shown that people with [major depressive disorder] engage in higher levels of sedentary behavior, and that cross-sectionally sedentary behavior, is positively associated with depression,” they added. “Meeting WHO recommended [physical activity] levels could be recommended ... to prevent the onset of depression.”
The investigators pointed out that one of the major limitations of the study was that participants’ depression and activity were self-reported, which could predispose results to over- or underreporting. They also pointed out that a strength of the study was its large sample size.
Mr. McDowell and his associates reported no conflicts of interest. The sponsors of The Irish Longitudinal Study of Ageing played no role in this study’s design, methods, subject recruitment, data collection, analysis, or preparation.
SOURCE: McDowell CP et al. Exp Gerontol. 2018 Oct 2;112:68-75.
FROM EXPERIMENTAL GERONTOLOGY
ICYMI: Alirocumab improves cardiovascular outcomes
Among patients in the ODYSSEY Outcomes trial who’d had an acute coronary syndrome, only 9.5% of the alirocumab group versus 11.1% of the placebo group experienced composite primary endpoint events – death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. Furthermore, the incidence of adverse events in both groups was similar, although the alirocumab group experienced more local injection-site reactions.
The ODYSSEY Outcomes primary results were published in the New England Journal of Medicine (2018 Nov 7; doi: 10.1056/NEJMoa1801174).
We covered the story last March, from the American College of Cardiology scientific sessions. Find our coverage at the link below:
https://www.mdedge.com/ecardiologynews/article/160512/acc-conference-coverage/odyssey-outcomes-trial-redefines-secondary.
Among patients in the ODYSSEY Outcomes trial who’d had an acute coronary syndrome, only 9.5% of the alirocumab group versus 11.1% of the placebo group experienced composite primary endpoint events – death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. Furthermore, the incidence of adverse events in both groups was similar, although the alirocumab group experienced more local injection-site reactions.
The ODYSSEY Outcomes primary results were published in the New England Journal of Medicine (2018 Nov 7; doi: 10.1056/NEJMoa1801174).
We covered the story last March, from the American College of Cardiology scientific sessions. Find our coverage at the link below:
https://www.mdedge.com/ecardiologynews/article/160512/acc-conference-coverage/odyssey-outcomes-trial-redefines-secondary.
Among patients in the ODYSSEY Outcomes trial who’d had an acute coronary syndrome, only 9.5% of the alirocumab group versus 11.1% of the placebo group experienced composite primary endpoint events – death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. Furthermore, the incidence of adverse events in both groups was similar, although the alirocumab group experienced more local injection-site reactions.
The ODYSSEY Outcomes primary results were published in the New England Journal of Medicine (2018 Nov 7; doi: 10.1056/NEJMoa1801174).
We covered the story last March, from the American College of Cardiology scientific sessions. Find our coverage at the link below:
https://www.mdedge.com/ecardiologynews/article/160512/acc-conference-coverage/odyssey-outcomes-trial-redefines-secondary.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
FDA approves Sympazan for Lennox-Gastaut syndrome
, according to a release from its developer. Final approval came after the orphan drug designation period for the previously marketed formulation, Onfi, came to an end in October.
LGS is a severe form of epilepsy; it can present with multiple types of seizures, as well as intellectual disabilities. Patients with LGS can have difficulty swallowing tablets or large volumes of oral suspension – which was previously the only way clobazam was delivered – because of physical limitations or behavioral or compliance issues. According to the press release from Aquestive Therapeutics, the Sympazan oral film might be able to get around those difficulties and reduce care burdens, especially with patients who are resistant to or even combative about treatment.
The approval is based on multiple pharmacokinetic studies that altogether showed that the oral film is bioequivalent to clobazam tablets and has a similar safety profile.
In a phase 3 study of 238 patients with LGS, clobazam tablets were shown to reduce drop seizures (those that involved falls) by 41% at low doses and by 68% at high doses versus a reduction of 12% seen with placebo (P less than .05 for all doses vs. placebo).
There is a risk of profound sedation when clobazam is used alongside benzodiazepines; there is also a risk of sedation and somnolence if it is used concomitantly with alcohol or other CNS depressants. Other risks associated with clobazam include suicidal ideation and behavior, serious dermatologic reactions, and physical and psychological dependence. The most common adverse reactions included constipation, pyrexia, lethargy, and drooling.
Full prescribing information can be found on the FDA website.
, according to a release from its developer. Final approval came after the orphan drug designation period for the previously marketed formulation, Onfi, came to an end in October.
LGS is a severe form of epilepsy; it can present with multiple types of seizures, as well as intellectual disabilities. Patients with LGS can have difficulty swallowing tablets or large volumes of oral suspension – which was previously the only way clobazam was delivered – because of physical limitations or behavioral or compliance issues. According to the press release from Aquestive Therapeutics, the Sympazan oral film might be able to get around those difficulties and reduce care burdens, especially with patients who are resistant to or even combative about treatment.
The approval is based on multiple pharmacokinetic studies that altogether showed that the oral film is bioequivalent to clobazam tablets and has a similar safety profile.
In a phase 3 study of 238 patients with LGS, clobazam tablets were shown to reduce drop seizures (those that involved falls) by 41% at low doses and by 68% at high doses versus a reduction of 12% seen with placebo (P less than .05 for all doses vs. placebo).
There is a risk of profound sedation when clobazam is used alongside benzodiazepines; there is also a risk of sedation and somnolence if it is used concomitantly with alcohol or other CNS depressants. Other risks associated with clobazam include suicidal ideation and behavior, serious dermatologic reactions, and physical and psychological dependence. The most common adverse reactions included constipation, pyrexia, lethargy, and drooling.
Full prescribing information can be found on the FDA website.
, according to a release from its developer. Final approval came after the orphan drug designation period for the previously marketed formulation, Onfi, came to an end in October.
LGS is a severe form of epilepsy; it can present with multiple types of seizures, as well as intellectual disabilities. Patients with LGS can have difficulty swallowing tablets or large volumes of oral suspension – which was previously the only way clobazam was delivered – because of physical limitations or behavioral or compliance issues. According to the press release from Aquestive Therapeutics, the Sympazan oral film might be able to get around those difficulties and reduce care burdens, especially with patients who are resistant to or even combative about treatment.
The approval is based on multiple pharmacokinetic studies that altogether showed that the oral film is bioequivalent to clobazam tablets and has a similar safety profile.
In a phase 3 study of 238 patients with LGS, clobazam tablets were shown to reduce drop seizures (those that involved falls) by 41% at low doses and by 68% at high doses versus a reduction of 12% seen with placebo (P less than .05 for all doses vs. placebo).
There is a risk of profound sedation when clobazam is used alongside benzodiazepines; there is also a risk of sedation and somnolence if it is used concomitantly with alcohol or other CNS depressants. Other risks associated with clobazam include suicidal ideation and behavior, serious dermatologic reactions, and physical and psychological dependence. The most common adverse reactions included constipation, pyrexia, lethargy, and drooling.
Full prescribing information can be found on the FDA website.
Age, insurance type tied to delay in pediatric febrile UTI treatment
even after adjustment for confounders, according to a report in the Journal of Pediatrics.
Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.
In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.
The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.
The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.
One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.
This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.
SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.
This article was updated 10/24/18.
even after adjustment for confounders, according to a report in the Journal of Pediatrics.
Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.
In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.
The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.
The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.
One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.
This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.
SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.
This article was updated 10/24/18.
even after adjustment for confounders, according to a report in the Journal of Pediatrics.
Stephanie W. Hum and Nader Shaikh, MD, MPH, of the University of Pittsburgh, drew from data provided by two studies, Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation. Specifically, they extracted data regarding patients’ age, sex, history of UTIs, ethnicity, race, insurance, household size, and duration of fever before initiation of antimicrobial therapy, as well as primary caregivers’ level of education and income. Some factors were analyzed because of associations seen in adult studies, and others because of concerns about access to care. In this analysis, the researchers defined “treatment delay” as the number of hours between onset of fever and initiation of antimicrobial treatment and, after exclusion of afebrile children and those with missing data, included 660 patients.
In univariate analysis, both older age and commercial insurance were found to be significantly associated with delays in treatment. Compared with time to treatment seen with younger children, treatment was delayed by an average of 26.2 hours in children aged 12 months and older (P less than .001). Patients with commercial insurance were treated a mean of 12.6 hours later than were those with noncommercial insurance (P = .002). These associations remained significant even after adjustment in a multivariable regression model for sex, history of UTIs, ethnicity, race, primary caregivers’ level of education, insurance, and income level.
The finding regarding age is consistent with a previous study, and Ms. Hum and Dr. Shaikh suggested it may reflect parents experiencing reduced urgency regarding febrile illnesses among older children. However, the researchers also noted that greater rates of renal scarring are seen in older children, so “it seems important to educate physicians, parents, and triage nurses about the importance of early evaluation of children with fever,” even those older than 12 months.
The finding regarding insurance status, however, is contrary to what studies in adult populations have found, as well as those in pediatric EDs. The researchers suggested that perhaps parents with noncommercial insurance are more likely to take their children to EDs, where testing can be done on-site 24 hours a day, rather than to private clinics, which often have to send out testing to off-site laboratories.
One of the strengths of the study is its relatively large sample size, they said. Among its weaknesses is that treatment delays were self-reported by parents and might be inaccurate and that information regarding location of initial evaluation was not gathered and could not be examined with other factors.
This study was supported by a T35 training grant from the National Institute of Diabetes and Digestive and Kidney Diseases, sponsored by Tom R. Kleyman, MD, chief of the renal-electrolyte division at the University of Pittsburgh. The authors declared no conflicts of interest.
SOURCE: Hum SW et al. J Pediatr. 2018 Oct 16. doi: 10.1016/j.jpeds.2018.09.029.
This article was updated 10/24/18.
FROM THE JOURNAL OF PEDIATRICS
FDA approves DNA-based blood type test
The for use in transfusion.
It’s the second molecular test for blood compatibility but the first to report genotype in its results, according to an announcement from the agency.
The test is important because it evaluates patients – especially those who receive repeated blood transfusions for conditions such as sickle cell anemia – for non-ABO antigens, but it does so without using antisera, which is sometimes unavailable.
A study found comparable performance between the ID CORE XT, licensed serologic reagents, and DNA sequencing tests, according to the FDA.
The ID CORE XT test is marketed by Progenika Biopharma, a Grifols company.
More information can be found in the full FDA press announcement.
The for use in transfusion.
It’s the second molecular test for blood compatibility but the first to report genotype in its results, according to an announcement from the agency.
The test is important because it evaluates patients – especially those who receive repeated blood transfusions for conditions such as sickle cell anemia – for non-ABO antigens, but it does so without using antisera, which is sometimes unavailable.
A study found comparable performance between the ID CORE XT, licensed serologic reagents, and DNA sequencing tests, according to the FDA.
The ID CORE XT test is marketed by Progenika Biopharma, a Grifols company.
More information can be found in the full FDA press announcement.
The for use in transfusion.
It’s the second molecular test for blood compatibility but the first to report genotype in its results, according to an announcement from the agency.
The test is important because it evaluates patients – especially those who receive repeated blood transfusions for conditions such as sickle cell anemia – for non-ABO antigens, but it does so without using antisera, which is sometimes unavailable.
A study found comparable performance between the ID CORE XT, licensed serologic reagents, and DNA sequencing tests, according to the FDA.
The ID CORE XT test is marketed by Progenika Biopharma, a Grifols company.
More information can be found in the full FDA press announcement.
FDA approves emicizumab for hemophilia A without inhibitors
The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for subcutaneous prophylactic treatment in hemophilia A without factor VIII inhibitors.
Genentech announced the new approval on Oct. 4 of this year. In 2017, the bispecific antibody, which targets both factors IXa and X, was approved for patients as young as newborns who had factor VIII inhibitors; the latest approval allows it to be used for patients without inhibitors as well.
The approval is based on a pair of trials. HAVEN 3 (NCT02847637) is a phase 3 trial in which investigators looked at emicizumab prophylaxis weekly or every other week, versus on-demand factor VIII treatment in patients without inhibitors. The study included 152 patients aged 12 years and older who were previously treated with factor VIII therapy.
Compared with patients not receiving prophylactic treatments, those receiving weekly doses had a 96% reduction in treated bleeds, and those receiving doses every other week saw a 97% reduction. Investigators also found that 55.6% of patients treated every week, 60% of those treated every other week, and 0% of those treated with no prophylaxis experienced zero bleeds; similarly, 91.7%, 94.3%, and 5.6% experienced three or fewer bleeds.
The single-arm HAVEN 4 (NCT03020160) trial evaluated dosing patients every 4 weeks among 48 patients aged 12 years and older, with or without inhibitors, and results showed that even that dosing regimen could lead to a clinically meaningful control of bleeds: 56.1% had no bleeds, and 90.2% had three or fewer bleeds.
The most common adverse reactions were joint pain, headache, and injection-site reaction. When emicizumab-kxwh is used with activated prothrombin complex concentrate, there’s a risk of thrombotic microangiopathy and thrombotic events. Full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for subcutaneous prophylactic treatment in hemophilia A without factor VIII inhibitors.
Genentech announced the new approval on Oct. 4 of this year. In 2017, the bispecific antibody, which targets both factors IXa and X, was approved for patients as young as newborns who had factor VIII inhibitors; the latest approval allows it to be used for patients without inhibitors as well.
The approval is based on a pair of trials. HAVEN 3 (NCT02847637) is a phase 3 trial in which investigators looked at emicizumab prophylaxis weekly or every other week, versus on-demand factor VIII treatment in patients without inhibitors. The study included 152 patients aged 12 years and older who were previously treated with factor VIII therapy.
Compared with patients not receiving prophylactic treatments, those receiving weekly doses had a 96% reduction in treated bleeds, and those receiving doses every other week saw a 97% reduction. Investigators also found that 55.6% of patients treated every week, 60% of those treated every other week, and 0% of those treated with no prophylaxis experienced zero bleeds; similarly, 91.7%, 94.3%, and 5.6% experienced three or fewer bleeds.
The single-arm HAVEN 4 (NCT03020160) trial evaluated dosing patients every 4 weeks among 48 patients aged 12 years and older, with or without inhibitors, and results showed that even that dosing regimen could lead to a clinically meaningful control of bleeds: 56.1% had no bleeds, and 90.2% had three or fewer bleeds.
The most common adverse reactions were joint pain, headache, and injection-site reaction. When emicizumab-kxwh is used with activated prothrombin complex concentrate, there’s a risk of thrombotic microangiopathy and thrombotic events. Full prescribing information can be found on the FDA website.
The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for subcutaneous prophylactic treatment in hemophilia A without factor VIII inhibitors.
Genentech announced the new approval on Oct. 4 of this year. In 2017, the bispecific antibody, which targets both factors IXa and X, was approved for patients as young as newborns who had factor VIII inhibitors; the latest approval allows it to be used for patients without inhibitors as well.
The approval is based on a pair of trials. HAVEN 3 (NCT02847637) is a phase 3 trial in which investigators looked at emicizumab prophylaxis weekly or every other week, versus on-demand factor VIII treatment in patients without inhibitors. The study included 152 patients aged 12 years and older who were previously treated with factor VIII therapy.
Compared with patients not receiving prophylactic treatments, those receiving weekly doses had a 96% reduction in treated bleeds, and those receiving doses every other week saw a 97% reduction. Investigators also found that 55.6% of patients treated every week, 60% of those treated every other week, and 0% of those treated with no prophylaxis experienced zero bleeds; similarly, 91.7%, 94.3%, and 5.6% experienced three or fewer bleeds.
The single-arm HAVEN 4 (NCT03020160) trial evaluated dosing patients every 4 weeks among 48 patients aged 12 years and older, with or without inhibitors, and results showed that even that dosing regimen could lead to a clinically meaningful control of bleeds: 56.1% had no bleeds, and 90.2% had three or fewer bleeds.
The most common adverse reactions were joint pain, headache, and injection-site reaction. When emicizumab-kxwh is used with activated prothrombin complex concentrate, there’s a risk of thrombotic microangiopathy and thrombotic events. Full prescribing information can be found on the FDA website.