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Mortality is high in pediatric superrefractory status epilepticus
BANGKOK – presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.
“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.
The study included 15 consecutive patients aged between 1 month and 17 years treated for superrefractory status epilepticus (SRSE) during 2011-2017 at the Chinese University of Hong Kong, where Dr. Yau practices. Seven children died during their index hospital admission, with a median time to death of 8 days. Two more died within several years post discharge.
Morbidity was substantial: At follow-up 1 year after the index episode of SRSE, two patients had a Glasgow Outcome Scale (GOS) score of 3, indicative of severe disability; three patients had moderate disability, with a GOS of 4; and two patients were in a vegetative state, with a GOS of 2, both of whom subsequently died of aspiration pneumonia. Only 1 of the 15 patients had a good recovery. Through 8 years of follow-up, all six survivors had epilepsy. Common nonneurologic deficits included a predisposition to a variety of infections.
By way of background, Dr. Yau noted that convulsive status epilepticus is the most common neurologic emergency in children, with an incidence of about 20 episodes per 100,000. Of affected children, 10%-40% develop refractory status, with reported mortality rates of 16%-43%. SRSE is a term reserved for persistent or recurrent seizures 24 hours or more after onset of general anesthesia for management of refractory status.
The impetus for Dr. Yau’s study was the dearth of data on SRSE in children. The literature consists of a few case series totaling well under 100 patients.
The Hong Kong case series included 15 patients with SRSE who had a median age of 7.9 years, only 1 of whom had preexisting epilepsy, a case of epileptic encephalopathy with severe developmental delay. Of the 15, 12 were boys. The patients were placed on a median of four antiepileptic drugs. Those who survived to discharge spent a median of 17.8 days under general anesthesia and 42.5 days in the pediatric ICU.
The SRSE etiologies included febrile infection–related epilepsy syndrome in two cases, four serious infections, four cases of autoimmune etiology, two cases of epileptic encephalopathy, one patient with hypoxia caused by severe croup, and two of unknown origin despite intensive work-up.
The four in-hospital deaths caused by acute cerebral edema occurred a median 6.5 days after admission. There were also two deaths because of uncontrolled sepsis and one because of intraventricular bleeding secondary to thrombotic thrombocytopenic purpura thought to have occurred as a complication of interactions between the numerous prescribed medications. All six children with an infectious or unknown etiology died in hospital, whereas none of those with an autoimmune etiology, epileptic encephalopathy, or hypoxia did. Duration of anesthesia did not predict mortality.
Other investigators have reported that younger age is associated with higher mortality, but that was not true in the Hong Kong experience. Neither of the two children aged less than 3 years died during their index hospitalization. All 7 deaths occurred in the 13 children age 3 years or older.
When asked whether she thought SRSE or the underlying disorder was the bigger contributor to mortality, Dr. Yau replied that she believes the prolonged refractory seizures may have worsened cerebral edema in some patients and thereby have been the cause of death.
She reported having no financial conflicts regarding her study.
BANGKOK – presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.
“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.
The study included 15 consecutive patients aged between 1 month and 17 years treated for superrefractory status epilepticus (SRSE) during 2011-2017 at the Chinese University of Hong Kong, where Dr. Yau practices. Seven children died during their index hospital admission, with a median time to death of 8 days. Two more died within several years post discharge.
Morbidity was substantial: At follow-up 1 year after the index episode of SRSE, two patients had a Glasgow Outcome Scale (GOS) score of 3, indicative of severe disability; three patients had moderate disability, with a GOS of 4; and two patients were in a vegetative state, with a GOS of 2, both of whom subsequently died of aspiration pneumonia. Only 1 of the 15 patients had a good recovery. Through 8 years of follow-up, all six survivors had epilepsy. Common nonneurologic deficits included a predisposition to a variety of infections.
By way of background, Dr. Yau noted that convulsive status epilepticus is the most common neurologic emergency in children, with an incidence of about 20 episodes per 100,000. Of affected children, 10%-40% develop refractory status, with reported mortality rates of 16%-43%. SRSE is a term reserved for persistent or recurrent seizures 24 hours or more after onset of general anesthesia for management of refractory status.
The impetus for Dr. Yau’s study was the dearth of data on SRSE in children. The literature consists of a few case series totaling well under 100 patients.
The Hong Kong case series included 15 patients with SRSE who had a median age of 7.9 years, only 1 of whom had preexisting epilepsy, a case of epileptic encephalopathy with severe developmental delay. Of the 15, 12 were boys. The patients were placed on a median of four antiepileptic drugs. Those who survived to discharge spent a median of 17.8 days under general anesthesia and 42.5 days in the pediatric ICU.
The SRSE etiologies included febrile infection–related epilepsy syndrome in two cases, four serious infections, four cases of autoimmune etiology, two cases of epileptic encephalopathy, one patient with hypoxia caused by severe croup, and two of unknown origin despite intensive work-up.
The four in-hospital deaths caused by acute cerebral edema occurred a median 6.5 days after admission. There were also two deaths because of uncontrolled sepsis and one because of intraventricular bleeding secondary to thrombotic thrombocytopenic purpura thought to have occurred as a complication of interactions between the numerous prescribed medications. All six children with an infectious or unknown etiology died in hospital, whereas none of those with an autoimmune etiology, epileptic encephalopathy, or hypoxia did. Duration of anesthesia did not predict mortality.
Other investigators have reported that younger age is associated with higher mortality, but that was not true in the Hong Kong experience. Neither of the two children aged less than 3 years died during their index hospitalization. All 7 deaths occurred in the 13 children age 3 years or older.
When asked whether she thought SRSE or the underlying disorder was the bigger contributor to mortality, Dr. Yau replied that she believes the prolonged refractory seizures may have worsened cerebral edema in some patients and thereby have been the cause of death.
She reported having no financial conflicts regarding her study.
BANGKOK – presented by Maggie Lo Yee Yau, MD, at the International Epilepsy Congress.
“Death in these children usually occurred within the first few days after admission to the pediatric ICU,” she said at the congress sponsored by the International League Against Epilepsy.
The study included 15 consecutive patients aged between 1 month and 17 years treated for superrefractory status epilepticus (SRSE) during 2011-2017 at the Chinese University of Hong Kong, where Dr. Yau practices. Seven children died during their index hospital admission, with a median time to death of 8 days. Two more died within several years post discharge.
Morbidity was substantial: At follow-up 1 year after the index episode of SRSE, two patients had a Glasgow Outcome Scale (GOS) score of 3, indicative of severe disability; three patients had moderate disability, with a GOS of 4; and two patients were in a vegetative state, with a GOS of 2, both of whom subsequently died of aspiration pneumonia. Only 1 of the 15 patients had a good recovery. Through 8 years of follow-up, all six survivors had epilepsy. Common nonneurologic deficits included a predisposition to a variety of infections.
By way of background, Dr. Yau noted that convulsive status epilepticus is the most common neurologic emergency in children, with an incidence of about 20 episodes per 100,000. Of affected children, 10%-40% develop refractory status, with reported mortality rates of 16%-43%. SRSE is a term reserved for persistent or recurrent seizures 24 hours or more after onset of general anesthesia for management of refractory status.
The impetus for Dr. Yau’s study was the dearth of data on SRSE in children. The literature consists of a few case series totaling well under 100 patients.
The Hong Kong case series included 15 patients with SRSE who had a median age of 7.9 years, only 1 of whom had preexisting epilepsy, a case of epileptic encephalopathy with severe developmental delay. Of the 15, 12 were boys. The patients were placed on a median of four antiepileptic drugs. Those who survived to discharge spent a median of 17.8 days under general anesthesia and 42.5 days in the pediatric ICU.
The SRSE etiologies included febrile infection–related epilepsy syndrome in two cases, four serious infections, four cases of autoimmune etiology, two cases of epileptic encephalopathy, one patient with hypoxia caused by severe croup, and two of unknown origin despite intensive work-up.
The four in-hospital deaths caused by acute cerebral edema occurred a median 6.5 days after admission. There were also two deaths because of uncontrolled sepsis and one because of intraventricular bleeding secondary to thrombotic thrombocytopenic purpura thought to have occurred as a complication of interactions between the numerous prescribed medications. All six children with an infectious or unknown etiology died in hospital, whereas none of those with an autoimmune etiology, epileptic encephalopathy, or hypoxia did. Duration of anesthesia did not predict mortality.
Other investigators have reported that younger age is associated with higher mortality, but that was not true in the Hong Kong experience. Neither of the two children aged less than 3 years died during their index hospitalization. All 7 deaths occurred in the 13 children age 3 years or older.
When asked whether she thought SRSE or the underlying disorder was the bigger contributor to mortality, Dr. Yau replied that she believes the prolonged refractory seizures may have worsened cerebral edema in some patients and thereby have been the cause of death.
She reported having no financial conflicts regarding her study.
REPORTING FROM IEC 2019
Dupilumab found effective for adolescents with moderate to severe AD
AUSTIN, TEX. – according to results of a phase 3 study.
“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”
The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.
For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.
At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).
In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).
Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.
Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.
Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.
On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.
The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.
AUSTIN, TEX. – according to results of a phase 3 study.
“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”
The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.
For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.
At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).
In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).
Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.
Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.
Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.
On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.
The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.
AUSTIN, TEX. – according to results of a phase 3 study.
“Dupilumab works as effectively in adolescents as in adults,” Randy Prescilla, MD, one of the study authors, said in an interview at the annual meeting of the Society for Pediatric Dermatology. “It gives us promise that we could go into other age groups with the same optimism. We are enrolling patients in even younger age groups.”
The double-blind, placebo-controlled study analyzed the efficacy and safety of dupilumab monotherapy in patients between the ages of 12 and 17 years with moderate to severe atopic dermatitis (AD) inadequately controlled with topical therapies. In the United States, dupilumab is approved for those aged 12 years and older with moderate to severe disease inadequately controlled by topical prescription treatments or when those therapies are not advisable.
For the 16-week study, Dr. Prescilla, global medical affairs director of pediatric dermatology for Sanofi Genzyme, and colleagues randomized 251 patients to one of three groups: dupilumab every 2 weeks (200 mg if baseline weight was less than 60 kg; 300 mg if that weight was 60 kg or more); 300 mg dupilumab every 4 weeks; or placebo every 2 weeks.
At week 16, a significantly higher proportion of patients in the two drug treatment groups had Investigator’s Global Assessment scores of 0/1, compared with those in the placebo group (24.4%, 17.9%, and 2.4%) as well as a significantly higher percentage of patients who achieved at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) score (41.5%, 38.1%, and 8.2%).
In addition, patients in the two drug treatment groups experienced improved percent change in least square-means on the EASI from baseline to week 16, compared with those in the placebo group (–65.9%, –64.8%, and –23.6%), the Peak Pruritus Numerical Rating Scale (–47.9%, –45.5%, and –19.0%), body surface area affected by AD (–30.1%, –33.4%, and –11.7%), and in the SCORing AD clinical tool (P less than .001 for all comparisons).
Between baseline and week 16, scores on the Children’s Dermatology Life Quality Index and Patient-Oriented Eczema Measure improved significantly in the two dupilumab groups, compared with the placebo group. The rate of skin infection was higher in the placebo group (20%), compared with 11% in the group that received dupilumab every 2 weeks and 13.3% in the group receiving the drug every 4 weeks.
Conjunctivitis occurred more frequently with dupilumab treatment (9.8% in the every-2-weeks dupilumab group, 10.8% in the every-4-weeks dupilumab group, and 4.7% in the placebo group) as did injection site reactions (8.5%, 6.0%, and 3.5%). Two adverse events, one of which was serious, occurred in the placebo group.
Dr. Prescilla acknowledged certain limitations of the study, including its small sample size and the fact that it was limited to 16 weeks. “However, smaller sample size and duration are typical for this type of study and in line with the study design of the SOLO 1 and SOLO 2 studies in adults,” he said.
On Aug. 6, the European Commission extended the marketing authorization for dupilumab in the European Union to include adolescents 12-17 years of age with moderate to severe atopic dermatitis who are candidates for systemic therapy. On the same day, Sanofi Genzyme and Regeneron announced positive topline results in a phase 3 trial in children aged 6-11 years with severe AD.
The study’s principal investigator was Amy S. Paller, MD. The study was funded by Sanofi Genzyme and Regeneron. Dr. Prescilla is an employee of Sanofi Genzyme.
REPORTING FROM SPD 2019
Can Remote Electrical Neuromodulation Help Acute Migraine?
Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:
- Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
- The pain relief of the active treatment was sustained 48 hours post-treatment.
- Incidence of device-related adverse events was low and similar between treatment groups.
Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.
Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:
- Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
- The pain relief of the active treatment was sustained 48 hours post-treatment.
- Incidence of device-related adverse events was low and similar between treatment groups.
Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.
Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:
- Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
- The pain relief of the active treatment was sustained 48 hours post-treatment.
- Incidence of device-related adverse events was low and similar between treatment groups.
Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.
Multiple Cranial Nerve Blocks in Patients With Chronic Headache
Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:
- Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
- Time to benefit was between 0.5 and 33.58 hours.
- Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.
Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121.
Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:
- Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
- Time to benefit was between 0.5 and 33.58 hours.
- Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.
Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121.
Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:
- Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
- Time to benefit was between 0.5 and 33.58 hours.
- Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.
Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121.
Brainstem Raphe and Depression in Patients With Migraine
Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:
- There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
- More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
- Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.
Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.
Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:
- There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
- More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
- Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.
Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.
Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:
- There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
- More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
- Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.
Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.
Developments in gastric cancer
In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).
Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.
GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).
Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.
On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.
On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.
In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).
Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.
GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).
Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.
On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.
On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.
In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).
Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.
GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).
Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.
On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.
On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.
Upper and lower gastroenterology – the state of the art
In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.
In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.
In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.
In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.
In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.
In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.
This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.
Favorable Ebola results lead to drug trial termination, new focus
An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.
Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.
The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.
As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.
The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.
“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.
The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).
An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.
Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.
The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.
As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.
The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.
“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.
The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).
An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.
Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.
The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.
As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.
The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.
“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.
The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).
Women underrepresented as oncology trial corresponding authors
Fewer than one in five oncologic phase 3 randomized controlled trials (RCTs) had female corresponding authors, but the proportion of women in this authorship role appears to be gradually increasing, investigators report.
“Through identification of the factors associated with gender disparities in RCT leadership, we hope that the academic oncology community will work to better understand and address the underlying reasons for such imbalances,” wrote Ethan B. Ludmir, MD, of the University of Texas MD Anderson Cancer Center, Houston, and associates. The report is in JAMA Oncology.
The authors searched ClinicalTrials.gov in late 2017 for all oncologic phase 3 RCTs. Of the 1,239 they initially turned up, the authors narrowed them down to the 598 that used multiple arms to test a therapeutic intervention, underwent peer review, and published results of primary endpoints. Among the trials, all published between 2003 and 2018, 17.9% had female corresponding authors.
Industry-funded trials, which comprised 77.8% of the sample, had half as many female corresponding authors (14.4%) as those not funded by industry (30.1%) (P less than .001), “possibly reflecting gender biases that are enhanced in the context of industry relationships with academic medicine,” the authors wrote. The opposite trend appeared in cooperative group trials, a quarter of which (25.9%) had female corresponding authors, compared with 14.3% of noncooperative trials (P = .001).
Trials for breast cancer and head and neck cancer were most likely to have female corresponding authors, while the trials with the lowest rates were those for gastrointestinal, genitourinary, and hematologic cancers (P less than .001). The researchers also found gender disparities in the type of intervention tested: Radiotherapy and supportive care studies were more likely to have female corresponding authors, yet none of the surgical trials had any (P less than .001).
In addition, female corresponding authorship was more likely when the institutions were based in the United States (n = 329) than when they were overseas (P = .001). Women were corresponding authors in 22.5% of U.S. studies and 20% of Canadian studies but only 12% of European trials and 2.3% of Asian trials (P = .001).
Within the United States, more than a third of studies from institutions in the Southeast had female corresponding authors (34.1%), followed by those in the Midwest (27.5%) and West (25.9%). Southwestern institutions were least likely to have female corresponding authors (8.7%). Approximately twice as many studies came from Northeastern institutions as from other regions (n = 112), but only 18.8% of these had female corresponding authors (P = .03).
The frequency of female corresponding authors has been increasing, however: The authors calculated a 1.2% increase each year, “echoing data showing an approximate 1.0% annual increase in the number of female academic hematologist-oncologists,” they noted. “However, the absolute female corresponding author rate for these trials is still lower than the percentage of female academic oncologists in this general study period, ranging from 27% in 2000 to 39% in 2015.”
SOURCE: Ludmir EB et al. JAMA Oncology. 8 Aug 2019. doi: 10.1001/jamaoncol.2019.2196.
Fewer than one in five oncologic phase 3 randomized controlled trials (RCTs) had female corresponding authors, but the proportion of women in this authorship role appears to be gradually increasing, investigators report.
“Through identification of the factors associated with gender disparities in RCT leadership, we hope that the academic oncology community will work to better understand and address the underlying reasons for such imbalances,” wrote Ethan B. Ludmir, MD, of the University of Texas MD Anderson Cancer Center, Houston, and associates. The report is in JAMA Oncology.
The authors searched ClinicalTrials.gov in late 2017 for all oncologic phase 3 RCTs. Of the 1,239 they initially turned up, the authors narrowed them down to the 598 that used multiple arms to test a therapeutic intervention, underwent peer review, and published results of primary endpoints. Among the trials, all published between 2003 and 2018, 17.9% had female corresponding authors.
Industry-funded trials, which comprised 77.8% of the sample, had half as many female corresponding authors (14.4%) as those not funded by industry (30.1%) (P less than .001), “possibly reflecting gender biases that are enhanced in the context of industry relationships with academic medicine,” the authors wrote. The opposite trend appeared in cooperative group trials, a quarter of which (25.9%) had female corresponding authors, compared with 14.3% of noncooperative trials (P = .001).
Trials for breast cancer and head and neck cancer were most likely to have female corresponding authors, while the trials with the lowest rates were those for gastrointestinal, genitourinary, and hematologic cancers (P less than .001). The researchers also found gender disparities in the type of intervention tested: Radiotherapy and supportive care studies were more likely to have female corresponding authors, yet none of the surgical trials had any (P less than .001).
In addition, female corresponding authorship was more likely when the institutions were based in the United States (n = 329) than when they were overseas (P = .001). Women were corresponding authors in 22.5% of U.S. studies and 20% of Canadian studies but only 12% of European trials and 2.3% of Asian trials (P = .001).
Within the United States, more than a third of studies from institutions in the Southeast had female corresponding authors (34.1%), followed by those in the Midwest (27.5%) and West (25.9%). Southwestern institutions were least likely to have female corresponding authors (8.7%). Approximately twice as many studies came from Northeastern institutions as from other regions (n = 112), but only 18.8% of these had female corresponding authors (P = .03).
The frequency of female corresponding authors has been increasing, however: The authors calculated a 1.2% increase each year, “echoing data showing an approximate 1.0% annual increase in the number of female academic hematologist-oncologists,” they noted. “However, the absolute female corresponding author rate for these trials is still lower than the percentage of female academic oncologists in this general study period, ranging from 27% in 2000 to 39% in 2015.”
SOURCE: Ludmir EB et al. JAMA Oncology. 8 Aug 2019. doi: 10.1001/jamaoncol.2019.2196.
Fewer than one in five oncologic phase 3 randomized controlled trials (RCTs) had female corresponding authors, but the proportion of women in this authorship role appears to be gradually increasing, investigators report.
“Through identification of the factors associated with gender disparities in RCT leadership, we hope that the academic oncology community will work to better understand and address the underlying reasons for such imbalances,” wrote Ethan B. Ludmir, MD, of the University of Texas MD Anderson Cancer Center, Houston, and associates. The report is in JAMA Oncology.
The authors searched ClinicalTrials.gov in late 2017 for all oncologic phase 3 RCTs. Of the 1,239 they initially turned up, the authors narrowed them down to the 598 that used multiple arms to test a therapeutic intervention, underwent peer review, and published results of primary endpoints. Among the trials, all published between 2003 and 2018, 17.9% had female corresponding authors.
Industry-funded trials, which comprised 77.8% of the sample, had half as many female corresponding authors (14.4%) as those not funded by industry (30.1%) (P less than .001), “possibly reflecting gender biases that are enhanced in the context of industry relationships with academic medicine,” the authors wrote. The opposite trend appeared in cooperative group trials, a quarter of which (25.9%) had female corresponding authors, compared with 14.3% of noncooperative trials (P = .001).
Trials for breast cancer and head and neck cancer were most likely to have female corresponding authors, while the trials with the lowest rates were those for gastrointestinal, genitourinary, and hematologic cancers (P less than .001). The researchers also found gender disparities in the type of intervention tested: Radiotherapy and supportive care studies were more likely to have female corresponding authors, yet none of the surgical trials had any (P less than .001).
In addition, female corresponding authorship was more likely when the institutions were based in the United States (n = 329) than when they were overseas (P = .001). Women were corresponding authors in 22.5% of U.S. studies and 20% of Canadian studies but only 12% of European trials and 2.3% of Asian trials (P = .001).
Within the United States, more than a third of studies from institutions in the Southeast had female corresponding authors (34.1%), followed by those in the Midwest (27.5%) and West (25.9%). Southwestern institutions were least likely to have female corresponding authors (8.7%). Approximately twice as many studies came from Northeastern institutions as from other regions (n = 112), but only 18.8% of these had female corresponding authors (P = .03).
The frequency of female corresponding authors has been increasing, however: The authors calculated a 1.2% increase each year, “echoing data showing an approximate 1.0% annual increase in the number of female academic hematologist-oncologists,” they noted. “However, the absolute female corresponding author rate for these trials is still lower than the percentage of female academic oncologists in this general study period, ranging from 27% in 2000 to 39% in 2015.”
SOURCE: Ludmir EB et al. JAMA Oncology. 8 Aug 2019. doi: 10.1001/jamaoncol.2019.2196.
FROM JAMA ONCOLOGY
Algorithm boosts MACE prediction in patients with chest pain
Adding electrocardiogram findings and clinical assessment to high-sensitivity cardiac troponin measurements in patients presenting with chest pain could improve predictions of their risk of 30-day major adverse cardiac events, particularly unstable angina, research suggests.
Investigators reported outcomes of a prospective study involving 3,123 patients with suspected acute myocardial infarction. The findings are in the Journal of the American College of Cardiology.
The aim of the researchers was to validate an extended algorithm that combined the European Society of Cardiology’s high-sensitivity cardiac troponin measurement at presentation and after 1 hour (ESC hs-cTn 0/1 h algorithm) with clinical assessment and ECG findings to aid prediction of major adverse cardiac events (MACE) within 30 days.
The clinical assessment involved the treating ED physician’s use of a visual analog scale to assess the patient’s pretest probability for an acute coronary syndrome (ACS), with a score above 70% qualifying as high likelihood.
The researchers found that the ESC hs-cTn 0/1 h algorithm alone triaged significantly more patients toward rule-out for MACE than did the extended algorithm (60% vs. 45%, P less than .001). This resulted in 487 patients being reclassified toward “observe” by the extended algorithm, and among this group the 30-day MACE rate was 1.1%.
However, the 30-day MACE rates were similar in the two groups – 0.6% among those ruled out by the ESC hs-cTn 0/1 h algorithm alone and 0.4% in those ruled out by the extended algorithm – resulting in a similar negative predictive value.
“These estimates will help clinicians to appropriately manage patients triaged toward rule-out according to the ESC hs-cTnT 0/1 h algorithm, in whom either the [visual analog scale] for ACS or the ECG still suggests the presence of an ACS,” wrote Thomas Nestelberger, MD, of the Cardiovascular Research Institute Basel (Switzerland) at the University of Basel, and coinvestigators.
The ESC hs-cTn 0/1 h algorithm also ruled in fewer patients than did the extended algorithm (16% vs. 26%, P less than .001), giving it a higher positive predictive value.
When the researchers added unstable angina to the major adverse cardiac event outcome, they found the ESC hs-cTn 0/1 h algorithm had a lower negative predictive value and a higher negative likelihood ratio compared with the extended algorithm for patients ruled out, but a higher positive predictive value and positive likelihood ratio for patients ruled in.
“Our findings corroborate and extend previous research regarding the development and validation of algorithms for the safe and effective rule-out and rule-in of MACE in patients with symptoms suggestive of AMI,” the authors wrote.
This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, Nanosphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.
SOURCE: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.
In patients presenting at the emergency department with chest pain, it’s important not only to diagnose acute myocardial infarction, but also to predict short-term risk of cardiac events to help guide management. This thoughtful and comprehensive analysis is the largest study assessing the added value of clinical and ECG assessment to the prognostication by high-sensitivity cardiac troponin algorithms in patients evaluated for chest pain. It reinforces the accuracy of hs-cTn at presentation and after 1 hour (ESC hs-cTn 0/1 h) algorithms to predict AMI and 30-day AMI-related events.
It is important to note that if unstable angina had been included as a major adverse cardiac event, the study would have found that the extended algorithm performs better than the hs-cTn 0/1 h algorithm in the prediction of this endpoint.
Germán Cediel, MD, is from Hospital Universitari Germans Trias i Pujol in Spain, Alfredo Bardají, MD, is from the Joan XXIII University Hospital in Spain, and José A. Barrabés, MD, is from Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona. The comments are adapted from an editorial (J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.05.065). The authors declared support from Instituto de Salud Carlos III, Spain, cofinanced by the European Regional Development Fund, and declared consultancies and educational activities with the pharmaceutical sector.
In patients presenting at the emergency department with chest pain, it’s important not only to diagnose acute myocardial infarction, but also to predict short-term risk of cardiac events to help guide management. This thoughtful and comprehensive analysis is the largest study assessing the added value of clinical and ECG assessment to the prognostication by high-sensitivity cardiac troponin algorithms in patients evaluated for chest pain. It reinforces the accuracy of hs-cTn at presentation and after 1 hour (ESC hs-cTn 0/1 h) algorithms to predict AMI and 30-day AMI-related events.
It is important to note that if unstable angina had been included as a major adverse cardiac event, the study would have found that the extended algorithm performs better than the hs-cTn 0/1 h algorithm in the prediction of this endpoint.
Germán Cediel, MD, is from Hospital Universitari Germans Trias i Pujol in Spain, Alfredo Bardají, MD, is from the Joan XXIII University Hospital in Spain, and José A. Barrabés, MD, is from Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona. The comments are adapted from an editorial (J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.05.065). The authors declared support from Instituto de Salud Carlos III, Spain, cofinanced by the European Regional Development Fund, and declared consultancies and educational activities with the pharmaceutical sector.
In patients presenting at the emergency department with chest pain, it’s important not only to diagnose acute myocardial infarction, but also to predict short-term risk of cardiac events to help guide management. This thoughtful and comprehensive analysis is the largest study assessing the added value of clinical and ECG assessment to the prognostication by high-sensitivity cardiac troponin algorithms in patients evaluated for chest pain. It reinforces the accuracy of hs-cTn at presentation and after 1 hour (ESC hs-cTn 0/1 h) algorithms to predict AMI and 30-day AMI-related events.
It is important to note that if unstable angina had been included as a major adverse cardiac event, the study would have found that the extended algorithm performs better than the hs-cTn 0/1 h algorithm in the prediction of this endpoint.
Germán Cediel, MD, is from Hospital Universitari Germans Trias i Pujol in Spain, Alfredo Bardají, MD, is from the Joan XXIII University Hospital in Spain, and José A. Barrabés, MD, is from Vall d’Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona. The comments are adapted from an editorial (J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.05.065). The authors declared support from Instituto de Salud Carlos III, Spain, cofinanced by the European Regional Development Fund, and declared consultancies and educational activities with the pharmaceutical sector.
Adding electrocardiogram findings and clinical assessment to high-sensitivity cardiac troponin measurements in patients presenting with chest pain could improve predictions of their risk of 30-day major adverse cardiac events, particularly unstable angina, research suggests.
Investigators reported outcomes of a prospective study involving 3,123 patients with suspected acute myocardial infarction. The findings are in the Journal of the American College of Cardiology.
The aim of the researchers was to validate an extended algorithm that combined the European Society of Cardiology’s high-sensitivity cardiac troponin measurement at presentation and after 1 hour (ESC hs-cTn 0/1 h algorithm) with clinical assessment and ECG findings to aid prediction of major adverse cardiac events (MACE) within 30 days.
The clinical assessment involved the treating ED physician’s use of a visual analog scale to assess the patient’s pretest probability for an acute coronary syndrome (ACS), with a score above 70% qualifying as high likelihood.
The researchers found that the ESC hs-cTn 0/1 h algorithm alone triaged significantly more patients toward rule-out for MACE than did the extended algorithm (60% vs. 45%, P less than .001). This resulted in 487 patients being reclassified toward “observe” by the extended algorithm, and among this group the 30-day MACE rate was 1.1%.
However, the 30-day MACE rates were similar in the two groups – 0.6% among those ruled out by the ESC hs-cTn 0/1 h algorithm alone and 0.4% in those ruled out by the extended algorithm – resulting in a similar negative predictive value.
“These estimates will help clinicians to appropriately manage patients triaged toward rule-out according to the ESC hs-cTnT 0/1 h algorithm, in whom either the [visual analog scale] for ACS or the ECG still suggests the presence of an ACS,” wrote Thomas Nestelberger, MD, of the Cardiovascular Research Institute Basel (Switzerland) at the University of Basel, and coinvestigators.
The ESC hs-cTn 0/1 h algorithm also ruled in fewer patients than did the extended algorithm (16% vs. 26%, P less than .001), giving it a higher positive predictive value.
When the researchers added unstable angina to the major adverse cardiac event outcome, they found the ESC hs-cTn 0/1 h algorithm had a lower negative predictive value and a higher negative likelihood ratio compared with the extended algorithm for patients ruled out, but a higher positive predictive value and positive likelihood ratio for patients ruled in.
“Our findings corroborate and extend previous research regarding the development and validation of algorithms for the safe and effective rule-out and rule-in of MACE in patients with symptoms suggestive of AMI,” the authors wrote.
This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, Nanosphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.
SOURCE: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.
Adding electrocardiogram findings and clinical assessment to high-sensitivity cardiac troponin measurements in patients presenting with chest pain could improve predictions of their risk of 30-day major adverse cardiac events, particularly unstable angina, research suggests.
Investigators reported outcomes of a prospective study involving 3,123 patients with suspected acute myocardial infarction. The findings are in the Journal of the American College of Cardiology.
The aim of the researchers was to validate an extended algorithm that combined the European Society of Cardiology’s high-sensitivity cardiac troponin measurement at presentation and after 1 hour (ESC hs-cTn 0/1 h algorithm) with clinical assessment and ECG findings to aid prediction of major adverse cardiac events (MACE) within 30 days.
The clinical assessment involved the treating ED physician’s use of a visual analog scale to assess the patient’s pretest probability for an acute coronary syndrome (ACS), with a score above 70% qualifying as high likelihood.
The researchers found that the ESC hs-cTn 0/1 h algorithm alone triaged significantly more patients toward rule-out for MACE than did the extended algorithm (60% vs. 45%, P less than .001). This resulted in 487 patients being reclassified toward “observe” by the extended algorithm, and among this group the 30-day MACE rate was 1.1%.
However, the 30-day MACE rates were similar in the two groups – 0.6% among those ruled out by the ESC hs-cTn 0/1 h algorithm alone and 0.4% in those ruled out by the extended algorithm – resulting in a similar negative predictive value.
“These estimates will help clinicians to appropriately manage patients triaged toward rule-out according to the ESC hs-cTnT 0/1 h algorithm, in whom either the [visual analog scale] for ACS or the ECG still suggests the presence of an ACS,” wrote Thomas Nestelberger, MD, of the Cardiovascular Research Institute Basel (Switzerland) at the University of Basel, and coinvestigators.
The ESC hs-cTn 0/1 h algorithm also ruled in fewer patients than did the extended algorithm (16% vs. 26%, P less than .001), giving it a higher positive predictive value.
When the researchers added unstable angina to the major adverse cardiac event outcome, they found the ESC hs-cTn 0/1 h algorithm had a lower negative predictive value and a higher negative likelihood ratio compared with the extended algorithm for patients ruled out, but a higher positive predictive value and positive likelihood ratio for patients ruled in.
“Our findings corroborate and extend previous research regarding the development and validation of algorithms for the safe and effective rule-out and rule-in of MACE in patients with symptoms suggestive of AMI,” the authors wrote.
This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, Nanosphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.
SOURCE: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point:
Major finding: High-sensitivity cardiac troponin measurements combined with ECG and clinical assessment can help rule out MACE and unstable angina.
Study details: A prospective study of 3,123 patients with suspected acute myocardial infarction.
Disclosures: This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, NanoSphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.
Source: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.