BARCELONA – A malfunctioning inhaler may have scotched the results of an intranasal insulin study for patients with early Alzheimer’s disease – but in an unexpected way.

Instead of doing poorly, patients using the faulty device actually experienced better outcomes than did those who entered the study later and used a more reliable inhaler, Suzanne Craft, PhD, said at the Clinical Trials on Alzheimer’s Disease conference.

A secondary analysis of the ViaNase device subgroup “replicated findings in our original studies,” which used the same atomizer, said Dr. Craft, a professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C. “We remain optimistic, but clearly we are at the beginning of understanding optimal insulin doses and delivery techniques for this population.”

The 289-patient, placebo-controlled study was predicated by a prior successful study by Dr. Craft and her colleagues, published in 2012 in JAMA Neurology. That trial randomized 104 patients with amnestic mild cognitive impairment (MCI) or mild-moderate Alzheimer’s to placebo or intranasal insulin 20 or 40 IU. After 4 months, subjects in both insulin groups showed preserved cognition and functional abilities, as well as increased cerebral glucose metabolism.

The ViaNase device was manufactured by Kurve Technology. But the company redesigned it for the new trial, adding an electronic timing component, which Dr. Craft said, was supposed to increase ease of use.

“Unfortunately, there were frequent malfunctions of this mechanism for the first 49 patients – so much so that we had to discontinue using the device and switch to a newer one,” for the other 240 patients in the study. This intranasal drug-delivery system, called the Precisions Olfactory Delivery (POD) device, is made by Impel NeuroPharma. Dr. Craft’s trial is its first investigation in patients with Alzheimer’s disease.

The new study randomized 289 patients with MCI or mild Alzheimer’s to twice-daily sprays with a placebo device, or to intranasal insulin 40 IU for 12 months, followed by a 6-month, open-label period. The primary outcome was the Alzheimer’s Disease Assessment Scale-Cognition measure (ADAS-Cog 12). Secondary outcomes were the Clinical Dementia Rating Scale sum of boxes (CDR-sb) a memory composite measure, activities of daily living, cerebrospinal fluid biomarkers, and MRI of the hippocampus and entorhinal cortex.

Because of the device problems, Dr. Craft conducted separate analyses for the user groups. The primary was an intent-to-treat (ITT), mixed-model, repeat-measures analysis of the 240 using the POD device. The model controlled for age, sex, genetic risk status, and investigation site. An exploratory ITT analysis looked only at the ADAS-Cog 12 in the 49 who used the ViaNase device. Patients were a mean of 71 years old, with a mean Mini Mental State Exam score of 25. About 42% were positive for the high-risk apolipoprotein E epsilon-4 allele.

At 12 months, there was no between-group difference on the ADAS-Cog 12 measure; both groups increased by about 4 points, indicating worsening. Nor were there any changes in any of the Alzheimer’s-related biomarkers: amyloid-beta 40 and 42, total tau, or phosphorylated tau. There was a small but statistically significant difference in the sizes of the hippocampus and entorhinal cortex.

The ViaNase group fared somewhat better in the secondary analysis of the ADAS-Cog12. The measure increased by about 5 points in the placebo group, and about 2.5 points in the insulin group. The significant separation was evident at 3 months and continued to widen over the course of the study.

Compliance was very good in the larger group – around 85%. It was lower in the ViaNase group, probably because of the device’s unreliability. Retention was good in both groups. There were no significant differences in adverse events and no obvious safety issues.

The 6-month, open-label period will close out before the end of the year. In the meantime, Dr. Craft is conducting additional subgroup analyses on the 12-month data.

Dr. Craft has served as a consultant for GlaxoSmithKline and Accera.

[email protected]

SOURCE: Craft S et al. J Prev Alz Dis 2018;5(S1):S9, Abstract OC2.

BARCELONA – A malfunctioning inhaler may have scotched the results of an intranasal insulin study for patients with early Alzheimer’s disease – but in an unexpected way.

Instead of doing poorly, patients using the faulty device actually experienced better outcomes than did those who entered the study later and used a more reliable inhaler, Suzanne Craft, PhD, said at the Clinical Trials on Alzheimer’s Disease conference.

A secondary analysis of the ViaNase device subgroup “replicated findings in our original studies,” which used the same atomizer, said Dr. Craft, a professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C. “We remain optimistic, but clearly we are at the beginning of understanding optimal insulin doses and delivery techniques for this population.”

The 289-patient, placebo-controlled study was predicated by a prior successful study by Dr. Craft and her colleagues, published in 2012 in JAMA Neurology. That trial randomized 104 patients with amnestic mild cognitive impairment (MCI) or mild-moderate Alzheimer’s to placebo or intranasal insulin 20 or 40 IU. After 4 months, subjects in both insulin groups showed preserved cognition and functional abilities, as well as increased cerebral glucose metabolism.

The ViaNase device was manufactured by Kurve Technology. But the company redesigned it for the new trial, adding an electronic timing component, which Dr. Craft said, was supposed to increase ease of use.

“Unfortunately, there were frequent malfunctions of this mechanism for the first 49 patients – so much so that we had to discontinue using the device and switch to a newer one,” for the other 240 patients in the study. This intranasal drug-delivery system, called the Precisions Olfactory Delivery (POD) device, is made by Impel NeuroPharma. Dr. Craft’s trial is its first investigation in patients with Alzheimer’s disease.

The new study randomized 289 patients with MCI or mild Alzheimer’s to twice-daily sprays with a placebo device, or to intranasal insulin 40 IU for 12 months, followed by a 6-month, open-label period. The primary outcome was the Alzheimer’s Disease Assessment Scale-Cognition measure (ADAS-Cog 12). Secondary outcomes were the Clinical Dementia Rating Scale sum of boxes (CDR-sb) a memory composite measure, activities of daily living, cerebrospinal fluid biomarkers, and MRI of the hippocampus and entorhinal cortex.

Because of the device problems, Dr. Craft conducted separate analyses for the user groups. The primary was an intent-to-treat (ITT), mixed-model, repeat-measures analysis of the 240 using the POD device. The model controlled for age, sex, genetic risk status, and investigation site. An exploratory ITT analysis looked only at the ADAS-Cog 12 in the 49 who used the ViaNase device. Patients were a mean of 71 years old, with a mean Mini Mental State Exam score of 25. About 42% were positive for the high-risk apolipoprotein E epsilon-4 allele.

At 12 months, there was no between-group difference on the ADAS-Cog 12 measure; both groups increased by about 4 points, indicating worsening. Nor were there any changes in any of the Alzheimer’s-related biomarkers: amyloid-beta 40 and 42, total tau, or phosphorylated tau. There was a small but statistically significant difference in the sizes of the hippocampus and entorhinal cortex.

The ViaNase group fared somewhat better in the secondary analysis of the ADAS-Cog12. The measure increased by about 5 points in the placebo group, and about 2.5 points in the insulin group. The significant separation was evident at 3 months and continued to widen over the course of the study.

Compliance was very good in the larger group – around 85%. It was lower in the ViaNase group, probably because of the device’s unreliability. Retention was good in both groups. There were no significant differences in adverse events and no obvious safety issues.

The 6-month, open-label period will close out before the end of the year. In the meantime, Dr. Craft is conducting additional subgroup analyses on the 12-month data.

Dr. Craft has served as a consultant for GlaxoSmithKline and Accera.

[email protected]

SOURCE: Craft S et al. J Prev Alz Dis 2018;5(S1):S9, Abstract OC2.

BARCELONA – A malfunctioning inhaler may have scotched the results of an intranasal insulin study for patients with early Alzheimer’s disease – but in an unexpected way.

Instead of doing poorly, patients using the faulty device actually experienced better outcomes than did those who entered the study later and used a more reliable inhaler, Suzanne Craft, PhD, said at the Clinical Trials on Alzheimer’s Disease conference.

A secondary analysis of the ViaNase device subgroup “replicated findings in our original studies,” which used the same atomizer, said Dr. Craft, a professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C. “We remain optimistic, but clearly we are at the beginning of understanding optimal insulin doses and delivery techniques for this population.”

The 289-patient, placebo-controlled study was predicated by a prior successful study by Dr. Craft and her colleagues, published in 2012 in JAMA Neurology. That trial randomized 104 patients with amnestic mild cognitive impairment (MCI) or mild-moderate Alzheimer’s to placebo or intranasal insulin 20 or 40 IU. After 4 months, subjects in both insulin groups showed preserved cognition and functional abilities, as well as increased cerebral glucose metabolism.

The ViaNase device was manufactured by Kurve Technology. But the company redesigned it for the new trial, adding an electronic timing component, which Dr. Craft said, was supposed to increase ease of use.

“Unfortunately, there were frequent malfunctions of this mechanism for the first 49 patients – so much so that we had to discontinue using the device and switch to a newer one,” for the other 240 patients in the study. This intranasal drug-delivery system, called the Precisions Olfactory Delivery (POD) device, is made by Impel NeuroPharma. Dr. Craft’s trial is its first investigation in patients with Alzheimer’s disease.

The new study randomized 289 patients with MCI or mild Alzheimer’s to twice-daily sprays with a placebo device, or to intranasal insulin 40 IU for 12 months, followed by a 6-month, open-label period. The primary outcome was the Alzheimer’s Disease Assessment Scale-Cognition measure (ADAS-Cog 12). Secondary outcomes were the Clinical Dementia Rating Scale sum of boxes (CDR-sb) a memory composite measure, activities of daily living, cerebrospinal fluid biomarkers, and MRI of the hippocampus and entorhinal cortex.

Because of the device problems, Dr. Craft conducted separate analyses for the user groups. The primary was an intent-to-treat (ITT), mixed-model, repeat-measures analysis of the 240 using the POD device. The model controlled for age, sex, genetic risk status, and investigation site. An exploratory ITT analysis looked only at the ADAS-Cog 12 in the 49 who used the ViaNase device. Patients were a mean of 71 years old, with a mean Mini Mental State Exam score of 25. About 42% were positive for the high-risk apolipoprotein E epsilon-4 allele.

At 12 months, there was no between-group difference on the ADAS-Cog 12 measure; both groups increased by about 4 points, indicating worsening. Nor were there any changes in any of the Alzheimer’s-related biomarkers: amyloid-beta 40 and 42, total tau, or phosphorylated tau. There was a small but statistically significant difference in the sizes of the hippocampus and entorhinal cortex.

The ViaNase group fared somewhat better in the secondary analysis of the ADAS-Cog12. The measure increased by about 5 points in the placebo group, and about 2.5 points in the insulin group. The significant separation was evident at 3 months and continued to widen over the course of the study.

Compliance was very good in the larger group – around 85%. It was lower in the ViaNase group, probably because of the device’s unreliability. Retention was good in both groups. There were no significant differences in adverse events and no obvious safety issues.

The 6-month, open-label period will close out before the end of the year. In the meantime, Dr. Craft is conducting additional subgroup analyses on the 12-month data.

Dr. Craft has served as a consultant for GlaxoSmithKline and Accera.

[email protected]

SOURCE: Craft S et al. J Prev Alz Dis 2018;5(S1):S9, Abstract OC2.

NEW ORLEANS – Concurrent surgical resection and implanted strip electrodes eliminated refractory focal seizures in two patients with focal cortical dysplasia and reduced them by 62% in a third patient, according a report presented at the annual meeting of the American Epilepsy Society.

None of the patients had been considered surgical candidates because their seizure foci were in eloquent cortical regions; if fully resected, patients would have experienced marked neurologic deficits. But the combination procedure of flanking the incomplete resected foci with implanted electrodes allowed neurosurgeons to remove less tissue, preserving function while effectively treating previously untreatable seizures, Emily Mirro said at the meeting.

The two-in-one technique makes good surgical sense for these patients, she said in an interview. “If we simply performed the resection and closed without implanting the electrodes, just waiting to see if seizures develop or not, then going back to implant the electrodes, the surgery is riskier and more difficult,” said Ms. Mirro, director of field clinical engineering for NeuroPace, which makes the stimulator system.

At the meeting, she presented three case studies on behalf of primary authors Lawrence Shuer, MD, and Babak Razavi, MD, PhD, both of Stanford (Calif.) University.

The first patient was a 26-year-old with a focal cortical dysplasia in the right parietal region, causing about six seizures each month. At the time of surgery, surgeons flanked the resected region with four cortical strip leads over sensory cortex. The RNS System detected the first postsurgical seizure 1 month afterward. Five months later, the system was enabled at 0.5 milliamps. For the next year, the patient received about 100 stimulations per day, amounting to a total daily stimulation time of about 20 seconds. Electrographic seizures did return, at which point the system increased neurostimulation to about 2,000 per day (a total stimulation time of about 7 minutes per day). At 1.3 years, the patient remains seizure free.

Patient two was a 20-year-old with a left frontal transmantle cortical dysplasia that involved the inferior frontal sulcus. The baseline seizure frequency was about two per day. Surgeons removed the dysplastic area with a 2.0 cm x 0.5 cm resection; the deficit was flanked with two left-front cortical strip leads. In the following 9 days, the patient experienced eight seizures. At 14 days out, the system was enabled at 1 milliamp. This patient became seizure free and remains so at 1.3 years, with about 100 stimulations per day to suppress electrographic abnormalities.

The third patient, also 20 years old, had a left-parietal resection to the margin of the motor cortex. The baseline seizure frequency was up to 150 nocturnal events per month and several seizures during each day as well. The resection was flanked by one strip lead over the motor cortex; one depth lead implanted into it. Immediately after surgery, the patient experienced both electrographic and clinical seizures. The stimulator was enabled a week after surgery at 0.5 milliamps; this was titrated to 3 milliamps over 1.4 years. At last follow-up, the patient had about a 62% reduction in seizure frequency; all are now nocturnal.

None of the patients experienced any peri- or postoperative surgical complications.

Ms. Mirro is an employee of NeuroPace.

[email protected]

SOURCE: Razavi B et al. AES 2018, Abstract 2.315

NEW ORLEANS – Concurrent surgical resection and implanted strip electrodes eliminated refractory focal seizures in two patients with focal cortical dysplasia and reduced them by 62% in a third patient, according a report presented at the annual meeting of the American Epilepsy Society.

None of the patients had been considered surgical candidates because their seizure foci were in eloquent cortical regions; if fully resected, patients would have experienced marked neurologic deficits. But the combination procedure of flanking the incomplete resected foci with implanted electrodes allowed neurosurgeons to remove less tissue, preserving function while effectively treating previously untreatable seizures, Emily Mirro said at the meeting.

The two-in-one technique makes good surgical sense for these patients, she said in an interview. “If we simply performed the resection and closed without implanting the electrodes, just waiting to see if seizures develop or not, then going back to implant the electrodes, the surgery is riskier and more difficult,” said Ms. Mirro, director of field clinical engineering for NeuroPace, which makes the stimulator system.

At the meeting, she presented three case studies on behalf of primary authors Lawrence Shuer, MD, and Babak Razavi, MD, PhD, both of Stanford (Calif.) University.

The first patient was a 26-year-old with a focal cortical dysplasia in the right parietal region, causing about six seizures each month. At the time of surgery, surgeons flanked the resected region with four cortical strip leads over sensory cortex. The RNS System detected the first postsurgical seizure 1 month afterward. Five months later, the system was enabled at 0.5 milliamps. For the next year, the patient received about 100 stimulations per day, amounting to a total daily stimulation time of about 20 seconds. Electrographic seizures did return, at which point the system increased neurostimulation to about 2,000 per day (a total stimulation time of about 7 minutes per day). At 1.3 years, the patient remains seizure free.

Patient two was a 20-year-old with a left frontal transmantle cortical dysplasia that involved the inferior frontal sulcus. The baseline seizure frequency was about two per day. Surgeons removed the dysplastic area with a 2.0 cm x 0.5 cm resection; the deficit was flanked with two left-front cortical strip leads. In the following 9 days, the patient experienced eight seizures. At 14 days out, the system was enabled at 1 milliamp. This patient became seizure free and remains so at 1.3 years, with about 100 stimulations per day to suppress electrographic abnormalities.

The third patient, also 20 years old, had a left-parietal resection to the margin of the motor cortex. The baseline seizure frequency was up to 150 nocturnal events per month and several seizures during each day as well. The resection was flanked by one strip lead over the motor cortex; one depth lead implanted into it. Immediately after surgery, the patient experienced both electrographic and clinical seizures. The stimulator was enabled a week after surgery at 0.5 milliamps; this was titrated to 3 milliamps over 1.4 years. At last follow-up, the patient had about a 62% reduction in seizure frequency; all are now nocturnal.

None of the patients experienced any peri- or postoperative surgical complications.

Ms. Mirro is an employee of NeuroPace.

[email protected]

SOURCE: Razavi B et al. AES 2018, Abstract 2.315

NEW ORLEANS – Concurrent surgical resection and implanted strip electrodes eliminated refractory focal seizures in two patients with focal cortical dysplasia and reduced them by 62% in a third patient, according a report presented at the annual meeting of the American Epilepsy Society.

None of the patients had been considered surgical candidates because their seizure foci were in eloquent cortical regions; if fully resected, patients would have experienced marked neurologic deficits. But the combination procedure of flanking the incomplete resected foci with implanted electrodes allowed neurosurgeons to remove less tissue, preserving function while effectively treating previously untreatable seizures, Emily Mirro said at the meeting.

The two-in-one technique makes good surgical sense for these patients, she said in an interview. “If we simply performed the resection and closed without implanting the electrodes, just waiting to see if seizures develop or not, then going back to implant the electrodes, the surgery is riskier and more difficult,” said Ms. Mirro, director of field clinical engineering for NeuroPace, which makes the stimulator system.

At the meeting, she presented three case studies on behalf of primary authors Lawrence Shuer, MD, and Babak Razavi, MD, PhD, both of Stanford (Calif.) University.

The first patient was a 26-year-old with a focal cortical dysplasia in the right parietal region, causing about six seizures each month. At the time of surgery, surgeons flanked the resected region with four cortical strip leads over sensory cortex. The RNS System detected the first postsurgical seizure 1 month afterward. Five months later, the system was enabled at 0.5 milliamps. For the next year, the patient received about 100 stimulations per day, amounting to a total daily stimulation time of about 20 seconds. Electrographic seizures did return, at which point the system increased neurostimulation to about 2,000 per day (a total stimulation time of about 7 minutes per day). At 1.3 years, the patient remains seizure free.

Patient two was a 20-year-old with a left frontal transmantle cortical dysplasia that involved the inferior frontal sulcus. The baseline seizure frequency was about two per day. Surgeons removed the dysplastic area with a 2.0 cm x 0.5 cm resection; the deficit was flanked with two left-front cortical strip leads. In the following 9 days, the patient experienced eight seizures. At 14 days out, the system was enabled at 1 milliamp. This patient became seizure free and remains so at 1.3 years, with about 100 stimulations per day to suppress electrographic abnormalities.

The third patient, also 20 years old, had a left-parietal resection to the margin of the motor cortex. The baseline seizure frequency was up to 150 nocturnal events per month and several seizures during each day as well. The resection was flanked by one strip lead over the motor cortex; one depth lead implanted into it. Immediately after surgery, the patient experienced both electrographic and clinical seizures. The stimulator was enabled a week after surgery at 0.5 milliamps; this was titrated to 3 milliamps over 1.4 years. At last follow-up, the patient had about a 62% reduction in seizure frequency; all are now nocturnal.

None of the patients experienced any peri- or postoperative surgical complications.

Ms. Mirro is an employee of NeuroPace.

[email protected]

SOURCE: Razavi B et al. AES 2018, Abstract 2.315

NASHVILLE – True post–bariatric surgery hyperinsulinemic hypoglycemia is rare among bariatric surgery patients, based on a decade’s worth of experience from the Mayo Clinic, Rochester, Minn.

Kari Oakes/MDedge News

Of 2,386 patients who had bariatric surgery at Mayo, 60 (2.6%) had a postsurgical diagnosis code associated with hypoglycemia in their medical record. However, just five of them (0.25%) had documentation meeting the criteria for Whipple’s Triad, which consists of low blood glucose levels, symptoms associated with the low glucose levels, and symptom resolution when glucose levels are corrected, Tiffany Cortes, MD, reported in an oral presentation at Obesity Week, which is presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery .

“Postbariatric hypoglycemia is an infrequent occurrence among patients who present with suspicious symptoms,” said Dr. Cortes, an endocrinology fellow at the clinic.

Post–bariatric surgery hypoglycemia is characterized by neuroglycopenia with a documented plasma glucose of less than 54 mg/dL with symptom resolution after a rise in glucose levels; neuroglycopenia that occurs 1-3 hours after a meal; and symptom onset more than 6 months after bariatric surgery, said Dr. Cortes.

Previous work had found that the overall prevalence of post–bariatric surgery hyperinsulinemic hypoglycemia ranged from 17%-34%, with severe symptoms seen in fewer than 1% of surgery recipients.

Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), may result in wide postprandial blood glucose excursions, with a spike occurring about 30 minutes after eating. For symptomatic individuals, this postprandial glucose peak will prompt an insulin surge followed by a rapid and steep decline in serum glucose.

Looking at Mayo Clinic medical records from mid-2008 to the end of 2017, Dr. Cortes and her colleagues wanted to determine the prevalence of hyperinsulinemic hypoglycemia in the bariatric surgery population.

Additionally, the researchers wanted to see how patients who presented with symptoms suspicious for the syndrome were evaluated and to understand the efficacy of treatments.

Patients who had a diagnosis of type 1 diabetes mellitus and those who were on insulin or sulfonylureas were excluded from the retrospective chart review.

Of the 60 patients evaluated in the endocrinology clinic for symptoms suspicious for hyperinsulinemic hypoglycemia, 51 (85%) were female, and 14 had a diagnosis of diabetes before surgery. Mean patient age at surgery was 43 years.

These symptomatic patients had a mean presurgical body mass index (BMI) of 42.8 kg/m² (range, 38.6-49.3 kg/m²). Their mean time to maximal weight loss was 1.3 years after surgery, with symptoms beginning at 1.4 years after surgery. Patients lost a mean 37.4% of their body mass to reach a mean nadir BMI of 26.2.

Overall, about two-thirds of the surgeries performed were RYGB. Of patients with hypoglycemic symptoms, 73.3% had an RYGB. Revision of gastric bypass was the next most common surgery, at 21.8% overall; these patients constituted 15% of the hypoglycemic symptom group.

Of the patients with symptoms, 80% noted symptoms only after eating, with half of patients describing symptoms coming on 1-3 hours after eating. A little over a third of the patients didn’t describe the exact timing of symptoms.

Just 20 patients had a complete hypoglycemia work up bundle documented in their medical record, said Dr. Cortes. This consisted of measures of serum glucose, insulin, and C-peptide levels. Of the 20 patients, 5 met Whipple’s Triad criteria, and 4 of these patients received a diagnosis of hyperinsulinemic hypoglycemia.

Two patients had a 72-hour fast, and neither of them met diagnostic criteria. Seventeen patients had a mixed meal tolerance test, with one individual meeting diagnostic criteria for and receiving a diagnosis of hypoinsulinemic hyperglycemia.

Of the five patients meeting diagnostic criteria (0.20% of surgical population), all had received RYGB, and two had previous weight loss procedures, said Dr. Cortes. For four of the patients, the surgical indication was weight loss; the other patient had an indication of gastroesophageal reflux disease (GERD).

“Dietary interventions are the most effective treatment” for post–bariatric surgery hyperinsulinemic hypoglycemia in the Mayo Clinic experience, said Dr. Cortes.

Turning to the investigators’ examination of treatment recommendations for the 60 patients who reported hypoglycemic symptoms, most (95%) received an initial recommendation to manage symptoms by diet changes.

Most patients (77%) had at least one follow-up visit, with over half of these patients (61%) reporting improvement in symptoms, and seven patients (16%) reporting resolution. Twelve patients (27%) either remained the same or had not had a recurrence of symptoms.

Medication was prescribed for 12 patients; of them, 8 received the alpha glucosidase inhibitor acarbose and 7 responded, according to the record review. No one reported worsening of symptoms on acarbose.

Other individual patients were prescribed octreotide alone, or octreotide, pasireotide, or diazoxide in combination with acarbose, with variable results.

Dr. Cortes reported no conflicts of interest and no external sources of funding.

[email protected]

SOURCE: Cortes T et al. Obesity Week 2018, Abstract T-OR-2015.

NASHVILLE – True post–bariatric surgery hyperinsulinemic hypoglycemia is rare among bariatric surgery patients, based on a decade’s worth of experience from the Mayo Clinic, Rochester, Minn.

Kari Oakes/MDedge News

Of 2,386 patients who had bariatric surgery at Mayo, 60 (2.6%) had a postsurgical diagnosis code associated with hypoglycemia in their medical record. However, just five of them (0.25%) had documentation meeting the criteria for Whipple’s Triad, which consists of low blood glucose levels, symptoms associated with the low glucose levels, and symptom resolution when glucose levels are corrected, Tiffany Cortes, MD, reported in an oral presentation at Obesity Week, which is presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery .

“Postbariatric hypoglycemia is an infrequent occurrence among patients who present with suspicious symptoms,” said Dr. Cortes, an endocrinology fellow at the clinic.

Post–bariatric surgery hypoglycemia is characterized by neuroglycopenia with a documented plasma glucose of less than 54 mg/dL with symptom resolution after a rise in glucose levels; neuroglycopenia that occurs 1-3 hours after a meal; and symptom onset more than 6 months after bariatric surgery, said Dr. Cortes.

Previous work had found that the overall prevalence of post–bariatric surgery hyperinsulinemic hypoglycemia ranged from 17%-34%, with severe symptoms seen in fewer than 1% of surgery recipients.

Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), may result in wide postprandial blood glucose excursions, with a spike occurring about 30 minutes after eating. For symptomatic individuals, this postprandial glucose peak will prompt an insulin surge followed by a rapid and steep decline in serum glucose.

Looking at Mayo Clinic medical records from mid-2008 to the end of 2017, Dr. Cortes and her colleagues wanted to determine the prevalence of hyperinsulinemic hypoglycemia in the bariatric surgery population.

Additionally, the researchers wanted to see how patients who presented with symptoms suspicious for the syndrome were evaluated and to understand the efficacy of treatments.

Patients who had a diagnosis of type 1 diabetes mellitus and those who were on insulin or sulfonylureas were excluded from the retrospective chart review.

Of the 60 patients evaluated in the endocrinology clinic for symptoms suspicious for hyperinsulinemic hypoglycemia, 51 (85%) were female, and 14 had a diagnosis of diabetes before surgery. Mean patient age at surgery was 43 years.

These symptomatic patients had a mean presurgical body mass index (BMI) of 42.8 kg/m² (range, 38.6-49.3 kg/m²). Their mean time to maximal weight loss was 1.3 years after surgery, with symptoms beginning at 1.4 years after surgery. Patients lost a mean 37.4% of their body mass to reach a mean nadir BMI of 26.2.

Overall, about two-thirds of the surgeries performed were RYGB. Of patients with hypoglycemic symptoms, 73.3% had an RYGB. Revision of gastric bypass was the next most common surgery, at 21.8% overall; these patients constituted 15% of the hypoglycemic symptom group.

Of the patients with symptoms, 80% noted symptoms only after eating, with half of patients describing symptoms coming on 1-3 hours after eating. A little over a third of the patients didn’t describe the exact timing of symptoms.

Just 20 patients had a complete hypoglycemia work up bundle documented in their medical record, said Dr. Cortes. This consisted of measures of serum glucose, insulin, and C-peptide levels. Of the 20 patients, 5 met Whipple’s Triad criteria, and 4 of these patients received a diagnosis of hyperinsulinemic hypoglycemia.

Two patients had a 72-hour fast, and neither of them met diagnostic criteria. Seventeen patients had a mixed meal tolerance test, with one individual meeting diagnostic criteria for and receiving a diagnosis of hypoinsulinemic hyperglycemia.

Of the five patients meeting diagnostic criteria (0.20% of surgical population), all had received RYGB, and two had previous weight loss procedures, said Dr. Cortes. For four of the patients, the surgical indication was weight loss; the other patient had an indication of gastroesophageal reflux disease (GERD).

“Dietary interventions are the most effective treatment” for post–bariatric surgery hyperinsulinemic hypoglycemia in the Mayo Clinic experience, said Dr. Cortes.

Turning to the investigators’ examination of treatment recommendations for the 60 patients who reported hypoglycemic symptoms, most (95%) received an initial recommendation to manage symptoms by diet changes.

Most patients (77%) had at least one follow-up visit, with over half of these patients (61%) reporting improvement in symptoms, and seven patients (16%) reporting resolution. Twelve patients (27%) either remained the same or had not had a recurrence of symptoms.

Medication was prescribed for 12 patients; of them, 8 received the alpha glucosidase inhibitor acarbose and 7 responded, according to the record review. No one reported worsening of symptoms on acarbose.

Other individual patients were prescribed octreotide alone, or octreotide, pasireotide, or diazoxide in combination with acarbose, with variable results.

Dr. Cortes reported no conflicts of interest and no external sources of funding.

[email protected]

SOURCE: Cortes T et al. Obesity Week 2018, Abstract T-OR-2015.

NASHVILLE – True post–bariatric surgery hyperinsulinemic hypoglycemia is rare among bariatric surgery patients, based on a decade’s worth of experience from the Mayo Clinic, Rochester, Minn.

Kari Oakes/MDedge News

Of 2,386 patients who had bariatric surgery at Mayo, 60 (2.6%) had a postsurgical diagnosis code associated with hypoglycemia in their medical record. However, just five of them (0.25%) had documentation meeting the criteria for Whipple’s Triad, which consists of low blood glucose levels, symptoms associated with the low glucose levels, and symptom resolution when glucose levels are corrected, Tiffany Cortes, MD, reported in an oral presentation at Obesity Week, which is presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery .

“Postbariatric hypoglycemia is an infrequent occurrence among patients who present with suspicious symptoms,” said Dr. Cortes, an endocrinology fellow at the clinic.

Post–bariatric surgery hypoglycemia is characterized by neuroglycopenia with a documented plasma glucose of less than 54 mg/dL with symptom resolution after a rise in glucose levels; neuroglycopenia that occurs 1-3 hours after a meal; and symptom onset more than 6 months after bariatric surgery, said Dr. Cortes.

Previous work had found that the overall prevalence of post–bariatric surgery hyperinsulinemic hypoglycemia ranged from 17%-34%, with severe symptoms seen in fewer than 1% of surgery recipients.

Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), may result in wide postprandial blood glucose excursions, with a spike occurring about 30 minutes after eating. For symptomatic individuals, this postprandial glucose peak will prompt an insulin surge followed by a rapid and steep decline in serum glucose.

Looking at Mayo Clinic medical records from mid-2008 to the end of 2017, Dr. Cortes and her colleagues wanted to determine the prevalence of hyperinsulinemic hypoglycemia in the bariatric surgery population.

Additionally, the researchers wanted to see how patients who presented with symptoms suspicious for the syndrome were evaluated and to understand the efficacy of treatments.

Patients who had a diagnosis of type 1 diabetes mellitus and those who were on insulin or sulfonylureas were excluded from the retrospective chart review.

Of the 60 patients evaluated in the endocrinology clinic for symptoms suspicious for hyperinsulinemic hypoglycemia, 51 (85%) were female, and 14 had a diagnosis of diabetes before surgery. Mean patient age at surgery was 43 years.

These symptomatic patients had a mean presurgical body mass index (BMI) of 42.8 kg/m² (range, 38.6-49.3 kg/m²). Their mean time to maximal weight loss was 1.3 years after surgery, with symptoms beginning at 1.4 years after surgery. Patients lost a mean 37.4% of their body mass to reach a mean nadir BMI of 26.2.

Overall, about two-thirds of the surgeries performed were RYGB. Of patients with hypoglycemic symptoms, 73.3% had an RYGB. Revision of gastric bypass was the next most common surgery, at 21.8% overall; these patients constituted 15% of the hypoglycemic symptom group.

Of the patients with symptoms, 80% noted symptoms only after eating, with half of patients describing symptoms coming on 1-3 hours after eating. A little over a third of the patients didn’t describe the exact timing of symptoms.

Just 20 patients had a complete hypoglycemia work up bundle documented in their medical record, said Dr. Cortes. This consisted of measures of serum glucose, insulin, and C-peptide levels. Of the 20 patients, 5 met Whipple’s Triad criteria, and 4 of these patients received a diagnosis of hyperinsulinemic hypoglycemia.

Two patients had a 72-hour fast, and neither of them met diagnostic criteria. Seventeen patients had a mixed meal tolerance test, with one individual meeting diagnostic criteria for and receiving a diagnosis of hypoinsulinemic hyperglycemia.

Of the five patients meeting diagnostic criteria (0.20% of surgical population), all had received RYGB, and two had previous weight loss procedures, said Dr. Cortes. For four of the patients, the surgical indication was weight loss; the other patient had an indication of gastroesophageal reflux disease (GERD).

“Dietary interventions are the most effective treatment” for post–bariatric surgery hyperinsulinemic hypoglycemia in the Mayo Clinic experience, said Dr. Cortes.

Turning to the investigators’ examination of treatment recommendations for the 60 patients who reported hypoglycemic symptoms, most (95%) received an initial recommendation to manage symptoms by diet changes.

Most patients (77%) had at least one follow-up visit, with over half of these patients (61%) reporting improvement in symptoms, and seven patients (16%) reporting resolution. Twelve patients (27%) either remained the same or had not had a recurrence of symptoms.

Medication was prescribed for 12 patients; of them, 8 received the alpha glucosidase inhibitor acarbose and 7 responded, according to the record review. No one reported worsening of symptoms on acarbose.

Other individual patients were prescribed octreotide alone, or octreotide, pasireotide, or diazoxide in combination with acarbose, with variable results.

Dr. Cortes reported no conflicts of interest and no external sources of funding.

[email protected]

SOURCE: Cortes T et al. Obesity Week 2018, Abstract T-OR-2015.

SAN DIEGO – In an ongoing phase 1 study, the oral FMS-like tyrosine kinase 3 (FLT3)/AXL inhibitor gilteritinib produced a response rate of more than 90% in newly diagnosed patients with acute myeloid leukemia (AML) with a FLT3 mutation.

The dose escalation/expansion study coupled the oral agent with induction and consolidation chemotherapy and was aimed at establishing the dosing and safety of gilteritinib.

The findings – reported at the annual meeting of the American Society of Hematology – mean that the FLT3 inhibitor will next be compared with the current standard of care, which has a 60%-65% remission rate, according to Keith W. Pratz, MD, of Johns Hopkins University in Baltimore.

“The later-phase clinical studies that we will be doing with gilteritinib will look to compare midostaurin-based chemotherapy with gilteritinib and looking for outcomes, with hopes of improving upon this 60%-65% remission rate,” Dr. Pratz said in a video interview.

Gilteritinib was recently approved by the Food and Drug Administration for relapsed/refractory AML patients with FLT3 mutations.

Dr. Pratz said the approval will provide a needed new treatment option in that patient population, which has had a low response rate to conventional therapy, in the range of 10%-15%.

“There really wasn’t a standard approved therapy prior to this and this will be what is given to most patients who have a FLT3 mutation and relapse,” he said.

Dr. Pratz reported consultancy and research funding from Astellas, which markets gilteritinib, as well as other companies.

[email protected]

SAN DIEGO – In an ongoing phase 1 study, the oral FMS-like tyrosine kinase 3 (FLT3)/AXL inhibitor gilteritinib produced a response rate of more than 90% in newly diagnosed patients with acute myeloid leukemia (AML) with a FLT3 mutation.

The dose escalation/expansion study coupled the oral agent with induction and consolidation chemotherapy and was aimed at establishing the dosing and safety of gilteritinib.

The findings – reported at the annual meeting of the American Society of Hematology – mean that the FLT3 inhibitor will next be compared with the current standard of care, which has a 60%-65% remission rate, according to Keith W. Pratz, MD, of Johns Hopkins University in Baltimore.

“The later-phase clinical studies that we will be doing with gilteritinib will look to compare midostaurin-based chemotherapy with gilteritinib and looking for outcomes, with hopes of improving upon this 60%-65% remission rate,” Dr. Pratz said in a video interview.

Gilteritinib was recently approved by the Food and Drug Administration for relapsed/refractory AML patients with FLT3 mutations.

Dr. Pratz said the approval will provide a needed new treatment option in that patient population, which has had a low response rate to conventional therapy, in the range of 10%-15%.

“There really wasn’t a standard approved therapy prior to this and this will be what is given to most patients who have a FLT3 mutation and relapse,” he said.

Dr. Pratz reported consultancy and research funding from Astellas, which markets gilteritinib, as well as other companies.

[email protected]

SAN DIEGO – In an ongoing phase 1 study, the oral FMS-like tyrosine kinase 3 (FLT3)/AXL inhibitor gilteritinib produced a response rate of more than 90% in newly diagnosed patients with acute myeloid leukemia (AML) with a FLT3 mutation.

The dose escalation/expansion study coupled the oral agent with induction and consolidation chemotherapy and was aimed at establishing the dosing and safety of gilteritinib.

The findings – reported at the annual meeting of the American Society of Hematology – mean that the FLT3 inhibitor will next be compared with the current standard of care, which has a 60%-65% remission rate, according to Keith W. Pratz, MD, of Johns Hopkins University in Baltimore.

“The later-phase clinical studies that we will be doing with gilteritinib will look to compare midostaurin-based chemotherapy with gilteritinib and looking for outcomes, with hopes of improving upon this 60%-65% remission rate,” Dr. Pratz said in a video interview.

Gilteritinib was recently approved by the Food and Drug Administration for relapsed/refractory AML patients with FLT3 mutations.

Dr. Pratz said the approval will provide a needed new treatment option in that patient population, which has had a low response rate to conventional therapy, in the range of 10%-15%.

“There really wasn’t a standard approved therapy prior to this and this will be what is given to most patients who have a FLT3 mutation and relapse,” he said.

Dr. Pratz reported consultancy and research funding from Astellas, which markets gilteritinib, as well as other companies.

[email protected]

SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.

M. Alexander Otto/MDedge News

Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.

Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.

In short, universal screening in the ED would keep people from falling through the cracks.

From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.

Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.

The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.

Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.

Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.

“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.

Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.

Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.

Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.

[email protected]

SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.

SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.

M. Alexander Otto/MDedge News

Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.

Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.

In short, universal screening in the ED would keep people from falling through the cracks.

From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.

Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.

The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.

Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.

Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.

“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.

Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.

Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.

Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.

[email protected]

SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.

SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.

M. Alexander Otto/MDedge News

Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.

Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.

In short, universal screening in the ED would keep people from falling through the cracks.

From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.

Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.

The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.

Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.

Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.

“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.

Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.

Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.

Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.

[email protected]

SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.

CHICAGO – Individuals with both elevated lipoprotein(a) levels and a family history of coronary heart disease are at a considerably higher long-term risk of atherosclerotic cardiovascular disease and coronary heart disease events than those with one risk factor alone, according to results from a large clinical study presented at the American Heart Association scientific sessions.

“Elevated lipoprotein(a) levels or a positive family history of coronary heart disease each is independently associated with cardiovascular disease risk,” said Anurag Mehta, MD, of Emory University School of Medicine, Atlanta. “This study showed that the presence of both an elevated Lp(a) level and a positive family history has an additive joint association with long-term cardiovascular risk.”

Dr. Mehta reported on an analysis of 12,149 individuals participating in the Atherosclerosis Risk in Communities (ARIC) study. All study participants were free of cardiovascular disease at the time of enrollment. The researchers measured Lp(a) levels and ascertained family history by self-report. Forty-four percent of the study participants had a family history of coronary heart disease (CHD), and 23% were black.

Median follow-up of study participants was 21 years, over which time 3,114 atherosclerotic cardiovascular disease (ASCVD) and 2,283 CHD events occurred.

Black participants had a significantly higher average plasma Lp(a) concentration than white persons, at 16.7 mg/dL vs. 5.7 mg/dL. However, plasma Lp(a) levels between participants with either a positive or a negative family history of CHD were similar on average, 7.6 mg/dL and 7.8 mg/dL, respectively.

The study pooled black and white ARIC participants by race-specific Lp(a) levels (quintiles) and stratified them into four different groups: 1. positive family history and an elevated race-specific Lp(a) level (quintile 5); 2. positive family history and nonelevated race-specific Lp(a) level (quintiles 1-4); 3. negative family history and elevated race-specific Lp(a) level; and 4. negative family history and nonelevated race-specific Lp(a) level. “There was an increase in the proportion of participants with a family history of CHD across race-specific Lp(a) quintiles, highlighting the fact that family history is associated with race-specific Lp(a) levels,” Dr. Mehta said.

“We observed that the ASCVD incidence was higher among participants with an elevated Lp(a) level or a family history of CHD as compared with participants with nonelevated Lp(a) levels and no family history,” Dr. Mehta said. “The highest ASCVD incidence was noted among participants with an elevated Lp(a) level as well as a positive family history.” Among those patients, the cumulative incidence of ASCVD events was nearly 25%, compared with 22% for those with a positive family history and nonelevated Lp(a) levels (group 2) or those with a negative family history but elevated Lp(a) levels (group 3), and 18% for those with negative family history and nonelevated Lp(a) levels.

Results for the cumulative incidence of coronary events trended similarly, Dr. Mehta noted: around 22% for group 1, 19% for group 2, 17% for group 3, and 14% for group 4.

“Having an elevated Lp(a) level as well as a family history of CHD was associated with a higher adjusted hazard for ASCVD and coronary events,” he said. Group 1 patients had a 43% greater risk for ASCVD and 68% greater risk for CHD, respectively, compared with a 16% and 30% greater risk for group 2, and 20% and 27% greater risk for group 3.

“Our findings indicate that these easily measurable nontraditional risk markers can help identify those at an elevated long-term CVD risk and may be useful for informing CVD prevention strategies among asymptomatic individuals,” Dr. Mehta said.

Dr. Mehta had no financial relationships to disclose.

SOURCE: Mehta A et al. AHA scientific sessions, Abstract AT.AOS.03 119.

CHICAGO – Individuals with both elevated lipoprotein(a) levels and a family history of coronary heart disease are at a considerably higher long-term risk of atherosclerotic cardiovascular disease and coronary heart disease events than those with one risk factor alone, according to results from a large clinical study presented at the American Heart Association scientific sessions.

“Elevated lipoprotein(a) levels or a positive family history of coronary heart disease each is independently associated with cardiovascular disease risk,” said Anurag Mehta, MD, of Emory University School of Medicine, Atlanta. “This study showed that the presence of both an elevated Lp(a) level and a positive family history has an additive joint association with long-term cardiovascular risk.”

Dr. Mehta reported on an analysis of 12,149 individuals participating in the Atherosclerosis Risk in Communities (ARIC) study. All study participants were free of cardiovascular disease at the time of enrollment. The researchers measured Lp(a) levels and ascertained family history by self-report. Forty-four percent of the study participants had a family history of coronary heart disease (CHD), and 23% were black.

Median follow-up of study participants was 21 years, over which time 3,114 atherosclerotic cardiovascular disease (ASCVD) and 2,283 CHD events occurred.

Black participants had a significantly higher average plasma Lp(a) concentration than white persons, at 16.7 mg/dL vs. 5.7 mg/dL. However, plasma Lp(a) levels between participants with either a positive or a negative family history of CHD were similar on average, 7.6 mg/dL and 7.8 mg/dL, respectively.

The study pooled black and white ARIC participants by race-specific Lp(a) levels (quintiles) and stratified them into four different groups: 1. positive family history and an elevated race-specific Lp(a) level (quintile 5); 2. positive family history and nonelevated race-specific Lp(a) level (quintiles 1-4); 3. negative family history and elevated race-specific Lp(a) level; and 4. negative family history and nonelevated race-specific Lp(a) level. “There was an increase in the proportion of participants with a family history of CHD across race-specific Lp(a) quintiles, highlighting the fact that family history is associated with race-specific Lp(a) levels,” Dr. Mehta said.

“We observed that the ASCVD incidence was higher among participants with an elevated Lp(a) level or a family history of CHD as compared with participants with nonelevated Lp(a) levels and no family history,” Dr. Mehta said. “The highest ASCVD incidence was noted among participants with an elevated Lp(a) level as well as a positive family history.” Among those patients, the cumulative incidence of ASCVD events was nearly 25%, compared with 22% for those with a positive family history and nonelevated Lp(a) levels (group 2) or those with a negative family history but elevated Lp(a) levels (group 3), and 18% for those with negative family history and nonelevated Lp(a) levels.

Results for the cumulative incidence of coronary events trended similarly, Dr. Mehta noted: around 22% for group 1, 19% for group 2, 17% for group 3, and 14% for group 4.

“Having an elevated Lp(a) level as well as a family history of CHD was associated with a higher adjusted hazard for ASCVD and coronary events,” he said. Group 1 patients had a 43% greater risk for ASCVD and 68% greater risk for CHD, respectively, compared with a 16% and 30% greater risk for group 2, and 20% and 27% greater risk for group 3.

“Our findings indicate that these easily measurable nontraditional risk markers can help identify those at an elevated long-term CVD risk and may be useful for informing CVD prevention strategies among asymptomatic individuals,” Dr. Mehta said.

Dr. Mehta had no financial relationships to disclose.

SOURCE: Mehta A et al. AHA scientific sessions, Abstract AT.AOS.03 119.

CHICAGO – Individuals with both elevated lipoprotein(a) levels and a family history of coronary heart disease are at a considerably higher long-term risk of atherosclerotic cardiovascular disease and coronary heart disease events than those with one risk factor alone, according to results from a large clinical study presented at the American Heart Association scientific sessions.

“Elevated lipoprotein(a) levels or a positive family history of coronary heart disease each is independently associated with cardiovascular disease risk,” said Anurag Mehta, MD, of Emory University School of Medicine, Atlanta. “This study showed that the presence of both an elevated Lp(a) level and a positive family history has an additive joint association with long-term cardiovascular risk.”

Dr. Mehta reported on an analysis of 12,149 individuals participating in the Atherosclerosis Risk in Communities (ARIC) study. All study participants were free of cardiovascular disease at the time of enrollment. The researchers measured Lp(a) levels and ascertained family history by self-report. Forty-four percent of the study participants had a family history of coronary heart disease (CHD), and 23% were black.

Median follow-up of study participants was 21 years, over which time 3,114 atherosclerotic cardiovascular disease (ASCVD) and 2,283 CHD events occurred.

Black participants had a significantly higher average plasma Lp(a) concentration than white persons, at 16.7 mg/dL vs. 5.7 mg/dL. However, plasma Lp(a) levels between participants with either a positive or a negative family history of CHD were similar on average, 7.6 mg/dL and 7.8 mg/dL, respectively.

The study pooled black and white ARIC participants by race-specific Lp(a) levels (quintiles) and stratified them into four different groups: 1. positive family history and an elevated race-specific Lp(a) level (quintile 5); 2. positive family history and nonelevated race-specific Lp(a) level (quintiles 1-4); 3. negative family history and elevated race-specific Lp(a) level; and 4. negative family history and nonelevated race-specific Lp(a) level. “There was an increase in the proportion of participants with a family history of CHD across race-specific Lp(a) quintiles, highlighting the fact that family history is associated with race-specific Lp(a) levels,” Dr. Mehta said.

“We observed that the ASCVD incidence was higher among participants with an elevated Lp(a) level or a family history of CHD as compared with participants with nonelevated Lp(a) levels and no family history,” Dr. Mehta said. “The highest ASCVD incidence was noted among participants with an elevated Lp(a) level as well as a positive family history.” Among those patients, the cumulative incidence of ASCVD events was nearly 25%, compared with 22% for those with a positive family history and nonelevated Lp(a) levels (group 2) or those with a negative family history but elevated Lp(a) levels (group 3), and 18% for those with negative family history and nonelevated Lp(a) levels.

Results for the cumulative incidence of coronary events trended similarly, Dr. Mehta noted: around 22% for group 1, 19% for group 2, 17% for group 3, and 14% for group 4.

“Having an elevated Lp(a) level as well as a family history of CHD was associated with a higher adjusted hazard for ASCVD and coronary events,” he said. Group 1 patients had a 43% greater risk for ASCVD and 68% greater risk for CHD, respectively, compared with a 16% and 30% greater risk for group 2, and 20% and 27% greater risk for group 3.

“Our findings indicate that these easily measurable nontraditional risk markers can help identify those at an elevated long-term CVD risk and may be useful for informing CVD prevention strategies among asymptomatic individuals,” Dr. Mehta said.

Dr. Mehta had no financial relationships to disclose.

SOURCE: Mehta A et al. AHA scientific sessions, Abstract AT.AOS.03 119.

How thorough are you when you prescribe medication? You check the patient’s list of allergies and current medications. You make sure that the dose is appropriate for the patient’s weight. Hopefully, you spend a minute or 2 describing the most common side effects. You prescribe the correct amount of medication and an appropriate number of refills. If you think you can distill it into one or two sentences, you also explain the medication’s mechanism of action. That is if you understand it yourself.

megaflopp/Thinkstock

What about placebos? How often do you believe that your patient has gotten better because of the placebo effect? Do you ever intentionally recommend or prescribe a placebo? Do you share with the patient that there is no current explanation of why the treatment you are recommending should work? Or, do you just play dumb?

Whether you admit to being a frequent prescriber of placebos or not you should take the 20 minutes it will take to read a New York Times article titled “What if the Placebo Effect Isn’t a Trick” (Gary Greenberg, Nov 7, 2018). You will learn a bit about the history of the placebo effect including some recent functional MRI studies that have uncovered consistent brain activity patterns in subjects that respond to placebos.

You will read about some exciting research indicating that certain people with a genomic variant of an enzyme that has been shown to affect the response to painkillers generally have the weakest response to placebo. While in some studies the association between the patient’s response and the level of the enzyme is the reverse, Kathryn Hall, PhD, the molecular biologist overseeing these studies, feels that at this point in her research the fact that there is an association that varies with genotype is a critical finding. She suspects that the placebo effect and the drug operate on the same biochemical highway that includes this enzyme and that “clinician warmth” is particularly effective in patients with a certain genotype.

Ted Kaptchuk, who heads up Harvard Medical School’s Program in Placebo Studies and the Therapeutic Encounter and has collaborated with Dr. Hall, hypothesizes “that the placebo effect is a biological response to an act of caring.” Is Dr. Hall’s work the first step in defining that response?

What does all of this new information mean for us as care dispensers? I think it means that caring is important and can make a critical difference if we have chosen a patient with the favorable genome. Of course, how are we to know whether we are working with such a patient? All the caring in the world may not change the outcome if we have selected incorrectly.

And then there is the other side of the practitioner-patient relationship and the definition and quantification of “caring.” Are there practitioners who are so inept and/or devoid of caring that even patients with the most favorable genome are not going to respond to their attempts at dispensing placebos?

Are there some practitioners who are born with a knack for caring? Can it be taught? Do we select for the quality of caring with the Medical College Admission Test (MCAT)? Do we weed out those who obviously don’t have it during their training?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

How thorough are you when you prescribe medication? You check the patient’s list of allergies and current medications. You make sure that the dose is appropriate for the patient’s weight. Hopefully, you spend a minute or 2 describing the most common side effects. You prescribe the correct amount of medication and an appropriate number of refills. If you think you can distill it into one or two sentences, you also explain the medication’s mechanism of action. That is if you understand it yourself.

megaflopp/Thinkstock

What about placebos? How often do you believe that your patient has gotten better because of the placebo effect? Do you ever intentionally recommend or prescribe a placebo? Do you share with the patient that there is no current explanation of why the treatment you are recommending should work? Or, do you just play dumb?

Whether you admit to being a frequent prescriber of placebos or not you should take the 20 minutes it will take to read a New York Times article titled “What if the Placebo Effect Isn’t a Trick” (Gary Greenberg, Nov 7, 2018). You will learn a bit about the history of the placebo effect including some recent functional MRI studies that have uncovered consistent brain activity patterns in subjects that respond to placebos.

You will read about some exciting research indicating that certain people with a genomic variant of an enzyme that has been shown to affect the response to painkillers generally have the weakest response to placebo. While in some studies the association between the patient’s response and the level of the enzyme is the reverse, Kathryn Hall, PhD, the molecular biologist overseeing these studies, feels that at this point in her research the fact that there is an association that varies with genotype is a critical finding. She suspects that the placebo effect and the drug operate on the same biochemical highway that includes this enzyme and that “clinician warmth” is particularly effective in patients with a certain genotype.

Ted Kaptchuk, who heads up Harvard Medical School’s Program in Placebo Studies and the Therapeutic Encounter and has collaborated with Dr. Hall, hypothesizes “that the placebo effect is a biological response to an act of caring.” Is Dr. Hall’s work the first step in defining that response?

What does all of this new information mean for us as care dispensers? I think it means that caring is important and can make a critical difference if we have chosen a patient with the favorable genome. Of course, how are we to know whether we are working with such a patient? All the caring in the world may not change the outcome if we have selected incorrectly.

And then there is the other side of the practitioner-patient relationship and the definition and quantification of “caring.” Are there practitioners who are so inept and/or devoid of caring that even patients with the most favorable genome are not going to respond to their attempts at dispensing placebos?

Are there some practitioners who are born with a knack for caring? Can it be taught? Do we select for the quality of caring with the Medical College Admission Test (MCAT)? Do we weed out those who obviously don’t have it during their training?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

How thorough are you when you prescribe medication? You check the patient’s list of allergies and current medications. You make sure that the dose is appropriate for the patient’s weight. Hopefully, you spend a minute or 2 describing the most common side effects. You prescribe the correct amount of medication and an appropriate number of refills. If you think you can distill it into one or two sentences, you also explain the medication’s mechanism of action. That is if you understand it yourself.

megaflopp/Thinkstock

What about placebos? How often do you believe that your patient has gotten better because of the placebo effect? Do you ever intentionally recommend or prescribe a placebo? Do you share with the patient that there is no current explanation of why the treatment you are recommending should work? Or, do you just play dumb?

Whether you admit to being a frequent prescriber of placebos or not you should take the 20 minutes it will take to read a New York Times article titled “What if the Placebo Effect Isn’t a Trick” (Gary Greenberg, Nov 7, 2018). You will learn a bit about the history of the placebo effect including some recent functional MRI studies that have uncovered consistent brain activity patterns in subjects that respond to placebos.

You will read about some exciting research indicating that certain people with a genomic variant of an enzyme that has been shown to affect the response to painkillers generally have the weakest response to placebo. While in some studies the association between the patient’s response and the level of the enzyme is the reverse, Kathryn Hall, PhD, the molecular biologist overseeing these studies, feels that at this point in her research the fact that there is an association that varies with genotype is a critical finding. She suspects that the placebo effect and the drug operate on the same biochemical highway that includes this enzyme and that “clinician warmth” is particularly effective in patients with a certain genotype.

Ted Kaptchuk, who heads up Harvard Medical School’s Program in Placebo Studies and the Therapeutic Encounter and has collaborated with Dr. Hall, hypothesizes “that the placebo effect is a biological response to an act of caring.” Is Dr. Hall’s work the first step in defining that response?

What does all of this new information mean for us as care dispensers? I think it means that caring is important and can make a critical difference if we have chosen a patient with the favorable genome. Of course, how are we to know whether we are working with such a patient? All the caring in the world may not change the outcome if we have selected incorrectly.

And then there is the other side of the practitioner-patient relationship and the definition and quantification of “caring.” Are there practitioners who are so inept and/or devoid of caring that even patients with the most favorable genome are not going to respond to their attempts at dispensing placebos?

Are there some practitioners who are born with a knack for caring? Can it be taught? Do we select for the quality of caring with the Medical College Admission Test (MCAT)? Do we weed out those who obviously don’t have it during their training?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

It was a dark and stormy night.

CatLane/gettyimages

OK, it was a warm and sunny afternoon. But Halloween was approaching. Strange things happen. Plus, the patient’s name was Ichabod ...

OK, his name was Jerry. Jerry came to Boston from Chula Taco, Calif., to study at CIT, the famed Boston Chipotle Institute of Technology. He’d finished 4 months of isotretinoin and needed one more.

I asked him to call iPledge to request a transfer to me. He called back later to say that iPledge told him his account was “inactive,” and he needed to be registered again. This seemed odd, since his pills had only run out 3 days before.

Having confirmed his name, address, telephone number, and the last four digits of his social security number, I tried enrolling him on iPledge at 5:30 p.m. (Cue: thunder and lightning), expecting to get a request for an override code. Instead the screen just asked for his iPledge number (you have to use the old one, you know). I called iPledge (my favorite pastime), identified myself by the usual means (Full name. iPledge ID number. Date of personal significance. Office telephone. Thank you. How can I help you?).

I explained my dilemma. The representative asked that I verify Jerry’s identity. I gave her his name, date of birth, and the last four of his social.

“We have his name and date of birth,” she said, “but the social security digits don’t match.” She asked for his phone number, but his Boston number didn’t match what she had. “Do you have his address?” she asked. I did not, since he’d given me his Boston address, not his California one.

I left her on hold and called Jerry on my cell. He confirmed that the social security digits he’d given me were correct. He gave me his mother’s cell phone number, but that also turned out not to be what iPledge had on file.

“What other identifying information can I give you?” I asked the iPledge rep. “How about his home address?” she said. Back to my cell: “Jerry, what’s your home address?” “It’s 2470 Chalupa Drive, Chula Taco, California 9090909-090909,” he said.

I repeated that to the iPledge representative. “Please hold a moment,” she said.

She was back. “The street address is correct,” she said, “The ZIP is correct. But the town is wrong.”

The town is wrong? If Jerry didn’t know either the last four of his social or his town, how did he get Amazon deliveries? Was this identity theft by an Accutane seeker? Maybe Jerry was really a Russian spy with dry lips posing as an acne patient! (Cue: screeches, howls, more thunder.)

“Can you tell me which town you have listed for him?” I asked iPledge.

“No,” she said, “because you haven’t identified him properly yet,” (emphasis added).

Back to the cell: “Jerry, are you sure you know what town you live in?” He insisted he did. (But then, so would a spy, wouldn’t he?)

In near despair, I returned to the iPledge rep. “I really want to get this patient his medication, “I said. “And I really want to go home. Can you help either of us?”

“Let me get my supervisor,” she said. “This may take a few minutes.” I hung up on Jerry and, in a blaze of multitasking, filled out three Prior Authorization forms for clindamycin gel.

“I found your patient,” said the rep, returning at last. “Not only that, I was able to reregister him in the iPledge program. Want to know his iPledge number?

Of course!

“Now that he’s registered,” I said, “could you give me the name of the town you have him listed as living in on Chalupa Drive?”

“Sure,” she said, “We have him in Rancho Carmen Miranda. Can help you with anything else today?”

“No, thanks ...”

“Would you be willing to take a 2-minute survey ...?”

“No, but thank you very much!” I said, hanging up in triumph. (Cue: sunshine, violins.)

Back to the cell: “Jerry, you’re in! Here’s your iPledge number.”

“Thanks, Doc.”

“By the way, Jerry, iPledge has you living in the town of Rancho Carmen Miranda. Do you live there?”

“No,” said Jerry. “I don’t.”

“Well, Jerry, for 1 more month, for federal purposes, you do!”

I’m sure there’s a good explanation for all this. I just don’t want to know it. Just pass the candy corn.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

It was a dark and stormy night.

CatLane/gettyimages

OK, it was a warm and sunny afternoon. But Halloween was approaching. Strange things happen. Plus, the patient’s name was Ichabod ...

OK, his name was Jerry. Jerry came to Boston from Chula Taco, Calif., to study at CIT, the famed Boston Chipotle Institute of Technology. He’d finished 4 months of isotretinoin and needed one more.

I asked him to call iPledge to request a transfer to me. He called back later to say that iPledge told him his account was “inactive,” and he needed to be registered again. This seemed odd, since his pills had only run out 3 days before.

Having confirmed his name, address, telephone number, and the last four digits of his social security number, I tried enrolling him on iPledge at 5:30 p.m. (Cue: thunder and lightning), expecting to get a request for an override code. Instead the screen just asked for his iPledge number (you have to use the old one, you know). I called iPledge (my favorite pastime), identified myself by the usual means (Full name. iPledge ID number. Date of personal significance. Office telephone. Thank you. How can I help you?).

I explained my dilemma. The representative asked that I verify Jerry’s identity. I gave her his name, date of birth, and the last four of his social.

“We have his name and date of birth,” she said, “but the social security digits don’t match.” She asked for his phone number, but his Boston number didn’t match what she had. “Do you have his address?” she asked. I did not, since he’d given me his Boston address, not his California one.

I left her on hold and called Jerry on my cell. He confirmed that the social security digits he’d given me were correct. He gave me his mother’s cell phone number, but that also turned out not to be what iPledge had on file.

“What other identifying information can I give you?” I asked the iPledge rep. “How about his home address?” she said. Back to my cell: “Jerry, what’s your home address?” “It’s 2470 Chalupa Drive, Chula Taco, California 9090909-090909,” he said.

I repeated that to the iPledge representative. “Please hold a moment,” she said.

She was back. “The street address is correct,” she said, “The ZIP is correct. But the town is wrong.”

The town is wrong? If Jerry didn’t know either the last four of his social or his town, how did he get Amazon deliveries? Was this identity theft by an Accutane seeker? Maybe Jerry was really a Russian spy with dry lips posing as an acne patient! (Cue: screeches, howls, more thunder.)

“Can you tell me which town you have listed for him?” I asked iPledge.

“No,” she said, “because you haven’t identified him properly yet,” (emphasis added).

Back to the cell: “Jerry, are you sure you know what town you live in?” He insisted he did. (But then, so would a spy, wouldn’t he?)

In near despair, I returned to the iPledge rep. “I really want to get this patient his medication, “I said. “And I really want to go home. Can you help either of us?”

“Let me get my supervisor,” she said. “This may take a few minutes.” I hung up on Jerry and, in a blaze of multitasking, filled out three Prior Authorization forms for clindamycin gel.

“I found your patient,” said the rep, returning at last. “Not only that, I was able to reregister him in the iPledge program. Want to know his iPledge number?

Of course!

“Now that he’s registered,” I said, “could you give me the name of the town you have him listed as living in on Chalupa Drive?”

“Sure,” she said, “We have him in Rancho Carmen Miranda. Can help you with anything else today?”

“No, thanks ...”

“Would you be willing to take a 2-minute survey ...?”

“No, but thank you very much!” I said, hanging up in triumph. (Cue: sunshine, violins.)

Back to the cell: “Jerry, you’re in! Here’s your iPledge number.”

“Thanks, Doc.”

“By the way, Jerry, iPledge has you living in the town of Rancho Carmen Miranda. Do you live there?”

“No,” said Jerry. “I don’t.”

“Well, Jerry, for 1 more month, for federal purposes, you do!”

I’m sure there’s a good explanation for all this. I just don’t want to know it. Just pass the candy corn.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

It was a dark and stormy night.

CatLane/gettyimages

OK, it was a warm and sunny afternoon. But Halloween was approaching. Strange things happen. Plus, the patient’s name was Ichabod ...

OK, his name was Jerry. Jerry came to Boston from Chula Taco, Calif., to study at CIT, the famed Boston Chipotle Institute of Technology. He’d finished 4 months of isotretinoin and needed one more.

I asked him to call iPledge to request a transfer to me. He called back later to say that iPledge told him his account was “inactive,” and he needed to be registered again. This seemed odd, since his pills had only run out 3 days before.

Having confirmed his name, address, telephone number, and the last four digits of his social security number, I tried enrolling him on iPledge at 5:30 p.m. (Cue: thunder and lightning), expecting to get a request for an override code. Instead the screen just asked for his iPledge number (you have to use the old one, you know). I called iPledge (my favorite pastime), identified myself by the usual means (Full name. iPledge ID number. Date of personal significance. Office telephone. Thank you. How can I help you?).

I explained my dilemma. The representative asked that I verify Jerry’s identity. I gave her his name, date of birth, and the last four of his social.

“We have his name and date of birth,” she said, “but the social security digits don’t match.” She asked for his phone number, but his Boston number didn’t match what she had. “Do you have his address?” she asked. I did not, since he’d given me his Boston address, not his California one.

I left her on hold and called Jerry on my cell. He confirmed that the social security digits he’d given me were correct. He gave me his mother’s cell phone number, but that also turned out not to be what iPledge had on file.

“What other identifying information can I give you?” I asked the iPledge rep. “How about his home address?” she said. Back to my cell: “Jerry, what’s your home address?” “It’s 2470 Chalupa Drive, Chula Taco, California 9090909-090909,” he said.

I repeated that to the iPledge representative. “Please hold a moment,” she said.

She was back. “The street address is correct,” she said, “The ZIP is correct. But the town is wrong.”

The town is wrong? If Jerry didn’t know either the last four of his social or his town, how did he get Amazon deliveries? Was this identity theft by an Accutane seeker? Maybe Jerry was really a Russian spy with dry lips posing as an acne patient! (Cue: screeches, howls, more thunder.)

“Can you tell me which town you have listed for him?” I asked iPledge.

“No,” she said, “because you haven’t identified him properly yet,” (emphasis added).

Back to the cell: “Jerry, are you sure you know what town you live in?” He insisted he did. (But then, so would a spy, wouldn’t he?)

In near despair, I returned to the iPledge rep. “I really want to get this patient his medication, “I said. “And I really want to go home. Can you help either of us?”

“Let me get my supervisor,” she said. “This may take a few minutes.” I hung up on Jerry and, in a blaze of multitasking, filled out three Prior Authorization forms for clindamycin gel.

“I found your patient,” said the rep, returning at last. “Not only that, I was able to reregister him in the iPledge program. Want to know his iPledge number?

Of course!

“Now that he’s registered,” I said, “could you give me the name of the town you have him listed as living in on Chalupa Drive?”

“Sure,” she said, “We have him in Rancho Carmen Miranda. Can help you with anything else today?”

“No, thanks ...”

“Would you be willing to take a 2-minute survey ...?”

“No, but thank you very much!” I said, hanging up in triumph. (Cue: sunshine, violins.)

Back to the cell: “Jerry, you’re in! Here’s your iPledge number.”

“Thanks, Doc.”

“By the way, Jerry, iPledge has you living in the town of Rancho Carmen Miranda. Do you live there?”

“No,” said Jerry. “I don’t.”

“Well, Jerry, for 1 more month, for federal purposes, you do!”

I’m sure there’s a good explanation for all this. I just don’t want to know it. Just pass the candy corn.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Cancer patients treated with the oral anticoagulant apixaban (Eliquis) had a lower rate of venous thromboembolism but a higher rate of major bleeding, according to data from the AVERT study.

In the placebo-controlled, double-blind trial, 574 ambulatory cancer patients who were at moderate to high risk of thromboembolism (Khorana risk score of 2 or more) and were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for 180 days. Over the 210-day study period, 12 patients (4.2%) in the apixaban group experienced a venous thromboembolism as did 28 patients (10.2%) in the placebo group, an adjusted 61% reduction in risk associated with anticoagulant therapy. The number needed to treat to prevent one venous thromboembolism was 17, Marc Carrier, MD, of the University of Ottawa, and his coauthors reported in the Dec. 4 edition of the New England Journal of Medicine.

“The treatment of venous thromboembolism with therapeutic anticoagulation is challenging in patients with cancer, because it often involves daily injections of low-molecular-weight heparin and is associated with a high risk of thromboembolism recurrence and serious bleeding complications,” they wrote. As an oral agent, apixaban offers a more convenient alternative.

The authors added that their study found more favorable benefits from anticoagulant therapy than had been seen in previous studies and suggested that this may be the result of using a different agent and a twice-daily dosing regimen.

In the AVERT study, the lower incidence of thromboembolism in the treatment arm was largely because of a reduction in pulmonary embolisms; there were 5 cases in the apixaban group, compared with 16 in the placebo group. The apixaban group experienced 7 cases of deep-vein thrombosis, and the placebo group experienced 12 cases.

During the treatment period, the placebo group had 20 venous thrombembolisms and the apixaban group had 3.

However the incidence of major bleeding was twice as high in the apixaban group: 10 patients (3.5%), compared with 5 (1.8%) in the placebo group (P = .046). The difference between the two groups was mostly based on an increased incidence of gastrointestinal bleeding, hematuria, and gynecologic bleeding among patients treated with apixaban.

None of the major bleeds affected critical organs in any patients. Most were category 2 bleeds, and three cases were judged to be clinical emergencies.

There were 62 deaths overall in the study – 35 in the apixaban group and 27 in the placebo group – and 87% of these deaths were related to the cancer.

Many patients in the study had advanced cancer, which was also the most common cause of death, the authors said. However, there was one death from pulmonary embolism in the placebo group. The dominant cancer types in the study participants were lymphoma, gynecologic, pancreatic, and lung cancers. Two-thirds of the patients in each group had a Khorana risk score of 2, and one patient in each group had a score of 5.

A different trial design and larger study would be needed to examine the impact of treatment on mortality and outcomes related to specific tumor types and chemotherapy regimens, the authors said.

They stressed that only 5.9% of patients in the study had renal dysfunction, so the study results cannot necessarily be applied to these patients more generally, especially as they are known to be at higher risk of bleeding.

The study was supported by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. Thirteen authors declared honoraria, grants or personal fees from the pharmaceutical industry unrelated to the study. Two declared grants from the study funders for the study; ten authors had no conflicts of interest to declare.
 

SOURCE: Carrier M et al. N Engl J Med. 2018 Dec 4. doi: 10.1056/NEJMoa1814468
 

Just when I thought that all the nonsense about the benefits of aspirin for the prevention of heart attack had been obliterated with a series of reports on its danger and lack of benefit, more fake news arrived in the form of a proposal by the Centers for Disease Control and Prevention.

It proclaimed that there were “213 million opportunities to improve cardiovascular risks in America,” one of which would be to change behavior so that 9 million Americans would take a daily baby aspirin (MMWR 2018 Sep 7;67[35];983–91). Although the proposed benefits of aspirin have been around for a long time, the major contemporary emphasis resulted from the report of the Physicians’ Heart Study in healthy men in 1989 that there was a decrease in fatal and nonfatal MIs as a result of taking daily aspirin. However, listed in a separate endpoint analysis, sudden death, for some reason not considered to be a fatal event, was twice as frequent in the aspirin treated group compared to the placebo, and when included with fatal events wiped out most of the benefit of aspirin (N Engl J Med. 1989 Jul 20;321:129-35). Ask your friends like I do, if they take a baby aspirin daily and they all smile innocently and complacently and say, “Yes.”

Over the intervening years, there has been a general jousting around the benefits of aspirin with conflicting data and little convincing evidence. With the recent publications, there seems to be at least some glimmer hope that the public and medicine may come to their collective senses. In a series of articles published from the ASPREE and ASCEND trials, which included 19,114 and 15,480 healthy and diabetic patients, respectively, there is little benefit and significant risks to taking aspirin, not the least of which is severe bleeding and cancer.

In the ASPREE trial of healthy elderly men over 70, aspirin has no effect on both total all-cause mortality and cardiovascular mortality and is associated with increased major bleeding. ASPREE also reported that, in healthy elderly men, aspirin was associated with an increase in mortality because of increased cancer incidence (N Engl J Med. 2018 Oct 18;379:1499-529).

The ASCEND trial, which included in the patients with diabetes and without evidence of coronary vascular disease, aspirin use as primary prevention was associated with a decrease in cardiovascular mortality, which was erased by an increase in serious bleeding (N Engl J Med. 2018 Oct 18; 379:1529-39). In a companion review, Paul M. Ridker, MD, of Brigham and Women’s Hospital, Boston, concludes that “the best strategy for the use of aspirin in the prevention of cardiovascular disease may simply be to prescribe a statin instead” (N Engl J Med 2018 Oct. 18; 379:1572-4)

Someone needs to call the CDC.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Just when I thought that all the nonsense about the benefits of aspirin for the prevention of heart attack had been obliterated with a series of reports on its danger and lack of benefit, more fake news arrived in the form of a proposal by the Centers for Disease Control and Prevention.

It proclaimed that there were “213 million opportunities to improve cardiovascular risks in America,” one of which would be to change behavior so that 9 million Americans would take a daily baby aspirin (MMWR 2018 Sep 7;67[35];983–91). Although the proposed benefits of aspirin have been around for a long time, the major contemporary emphasis resulted from the report of the Physicians’ Heart Study in healthy men in 1989 that there was a decrease in fatal and nonfatal MIs as a result of taking daily aspirin. However, listed in a separate endpoint analysis, sudden death, for some reason not considered to be a fatal event, was twice as frequent in the aspirin treated group compared to the placebo, and when included with fatal events wiped out most of the benefit of aspirin (N Engl J Med. 1989 Jul 20;321:129-35). Ask your friends like I do, if they take a baby aspirin daily and they all smile innocently and complacently and say, “Yes.”

Over the intervening years, there has been a general jousting around the benefits of aspirin with conflicting data and little convincing evidence. With the recent publications, there seems to be at least some glimmer hope that the public and medicine may come to their collective senses. In a series of articles published from the ASPREE and ASCEND trials, which included 19,114 and 15,480 healthy and diabetic patients, respectively, there is little benefit and significant risks to taking aspirin, not the least of which is severe bleeding and cancer.

In the ASPREE trial of healthy elderly men over 70, aspirin has no effect on both total all-cause mortality and cardiovascular mortality and is associated with increased major bleeding. ASPREE also reported that, in healthy elderly men, aspirin was associated with an increase in mortality because of increased cancer incidence (N Engl J Med. 2018 Oct 18;379:1499-529).

The ASCEND trial, which included in the patients with diabetes and without evidence of coronary vascular disease, aspirin use as primary prevention was associated with a decrease in cardiovascular mortality, which was erased by an increase in serious bleeding (N Engl J Med. 2018 Oct 18; 379:1529-39). In a companion review, Paul M. Ridker, MD, of Brigham and Women’s Hospital, Boston, concludes that “the best strategy for the use of aspirin in the prevention of cardiovascular disease may simply be to prescribe a statin instead” (N Engl J Med 2018 Oct. 18; 379:1572-4)

Someone needs to call the CDC.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Just when I thought that all the nonsense about the benefits of aspirin for the prevention of heart attack had been obliterated with a series of reports on its danger and lack of benefit, more fake news arrived in the form of a proposal by the Centers for Disease Control and Prevention.

It proclaimed that there were “213 million opportunities to improve cardiovascular risks in America,” one of which would be to change behavior so that 9 million Americans would take a daily baby aspirin (MMWR 2018 Sep 7;67[35];983–91). Although the proposed benefits of aspirin have been around for a long time, the major contemporary emphasis resulted from the report of the Physicians’ Heart Study in healthy men in 1989 that there was a decrease in fatal and nonfatal MIs as a result of taking daily aspirin. However, listed in a separate endpoint analysis, sudden death, for some reason not considered to be a fatal event, was twice as frequent in the aspirin treated group compared to the placebo, and when included with fatal events wiped out most of the benefit of aspirin (N Engl J Med. 1989 Jul 20;321:129-35). Ask your friends like I do, if they take a baby aspirin daily and they all smile innocently and complacently and say, “Yes.”

Over the intervening years, there has been a general jousting around the benefits of aspirin with conflicting data and little convincing evidence. With the recent publications, there seems to be at least some glimmer hope that the public and medicine may come to their collective senses. In a series of articles published from the ASPREE and ASCEND trials, which included 19,114 and 15,480 healthy and diabetic patients, respectively, there is little benefit and significant risks to taking aspirin, not the least of which is severe bleeding and cancer.

In the ASPREE trial of healthy elderly men over 70, aspirin has no effect on both total all-cause mortality and cardiovascular mortality and is associated with increased major bleeding. ASPREE also reported that, in healthy elderly men, aspirin was associated with an increase in mortality because of increased cancer incidence (N Engl J Med. 2018 Oct 18;379:1499-529).

The ASCEND trial, which included in the patients with diabetes and without evidence of coronary vascular disease, aspirin use as primary prevention was associated with a decrease in cardiovascular mortality, which was erased by an increase in serious bleeding (N Engl J Med. 2018 Oct 18; 379:1529-39). In a companion review, Paul M. Ridker, MD, of Brigham and Women’s Hospital, Boston, concludes that “the best strategy for the use of aspirin in the prevention of cardiovascular disease may simply be to prescribe a statin instead” (N Engl J Med 2018 Oct. 18; 379:1572-4)

Someone needs to call the CDC.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.