LAS VEGAS – Increased rates of persistent neonatal pulmonary hypertension in neonates put the brakes on STRIDER, an international placebo-controlled study looking at sildenafil as a treatment for early-onset intrauterine growth restriction (IUGR).

stockce/Thinkstock

The study’s independent data safety monitoring board halted STRIDER (Sildenafil Therapy in Dismal Prognosis Early-Onset Fetal Growth Restriction) last July, after an interim safety analysis identified possible fetal harm and no signal of benefit over placebo, Dr. Anouk Pels reported at the annual meeting of the Society for Maternal-Fetal Medicine. The late-breaking presentation at the meeting revealed the first outcome data details.

The board had “serious concerns that sildenafil may cause harm to newborn children. … Given the results , it is extremely unlikely that any benefit could be shown on the primary endpoint if the trial is continued to its completion,” said Dr. Pels of the University of Amsterdam. “Our recommendation is not to use sildenafil for this indication in pregnant women.”

Although the link remains as-yet unproven, pulmonary hypertension among sildenafil-exposed neonates is biologically plausible, she said. It could have been a symptomatic rebound response to the discontinuation of constant intrauterine sildenafil exposure – or it could have been a hint of something more profound. Like the genital vasculature, pulmonary vasculature is a target of the drug. Intrauterine exposure to sildenafil could theoretically alter its development.

“It’s possible that sildenafil may be causing structural changes in the pulmonary vasculature of fetuses. This needs to be explored further, and we will do so by performing additional analyses on autopsy data and placental histology.”

STRIDER involved 261 pregnant women diagnosed with severe early-onset fetal growth restriction. They were randomized to sildenafil 25 mg or placebo three times daily until delivery or 32 weeks’ gestation. A safety analysis was conducted after every 50 patients were enrolled. The preplanned interim analysis was conducted after half of the cohort had been enrolled and received at least one dose of the study medication.

The primary outcome was a composite measure of neonatal mortality or major neonatal morbidity at hospital discharge.

Gestational age at baseline was about 24.6 weeks, and the estimated fetal weight by ultrasound, 465 g. About 45% of pregnancies had evidence of a notching in the uterine artery. In about 42%, the pulsatility index of the umbilical artery was above the 95th percentile; the pulsatility index of the middle cerebral artery was below the 5% percentile in about 70% of cases.

About a quarter of the women had a diagnosis of pregnancy-induced hypertension, and another quarter, preeclampsia. Women used the study medication for a mean of 22 days.

There were no significant between-group differences in maternal outcomes. Median gestational age at delivery was 28 weeks in both groups. About 10% in each group experienced new-onset pregnancy-induced hypertension; About a quarter of each group developed new-onset preeclampsia or HELLP (hemolysis, elevated liver enzymes, low platelet count). There were no between-group differences in the number of maternal antihypertensives prescribed.

The primary combined outcome of neonatal mortality or major neonatal morbidity occurred in 66 of the sildenafil-exposed neonates and 58 of the placebo-exposed infants (61% vs. 54%) – not a significant difference. Fetal death occurred in 23 and 29 pregnancies, respectively (21% and 27%); neonatal death occurred in 21 and 11, respectively (19% and 10%). Overall, fetal/neonatal mortality was similar between the sildenafil and placebo groups (41% and 37%, respectively).

Of the 64 sildenafil-exposed neonates who survived to hospital discharge, 22 exhibited clinically relevant morbidity. Of the 67 in the placebo-treated group who survived to hospital discharge, 18 had clinically relevant morbidity. Overall, 42 in the sildenafil group and 49 of the placebo group survived to hospital discharge without relevant morbidity.

There were a number of secondary outcomes, none exhibiting any significant between-group differences. These included the median weights of those who experienced intrauterine death (425 g and 350 g), median live birth weight (725 g and 783 g), intraventricular hemorrhage of grade II or IV (3% and 2%), periventricular hemorrhage grade II or higher (0%, both groups), necrotizing enterocolitis grade II or higher (7% and 8%), and at least one culture-proven or clinical infection (41% and 33%).

The significantly higher rates of pulmonary hypertension in the sildenafil-exposed neonates was the showstopper. Almost half of the 21 who died had proven pulmonary hypertension (10), as did 6 of the 64 who survived – an excess of 16 cases. Of proven cases, 11 were persistent pulmonary hypertension. There were also two cases of sepsis-associated pulmonary hypertension and four cases of bronchopulmonary dysplasia associated with the disorder. In the placebo-exposed group, pulmonary hypertension occurred in 3 of the 11 deaths and 1 of the 67 who survived. Of proven cases, two were persistent pulmonary hypertension. There was no sepsis-associated pulmonary hypertension, but there were three cases of bronchopulmonary dysplasia associated with the disorder. Some children had both persistent pulmonary hypertension and bronchopulmonary dysplasia.

“While there was no difference in the primary outcomes or in overall mortality, there were more cases of pulmonary hypertension in the sildenafil group,” Dr. Pels said. “We can speculate on the cause, whether it was related to sildenafil and why, or whether it was simply chance. This is the reason we need to conduct more in-depth analyses of these data.”

Funding came from federal health agencies and universities in the countries where STRIDER was conducted, including New Zealand, Australia, the United Kingdom, Ireland, and the Netherlands. Dr. Pels had no relevant financial disclosures.

SOURCE: Pels A et al. The Pregnancy Meeting, Late-Breaker 2.

LAS VEGAS – Increased rates of persistent neonatal pulmonary hypertension in neonates put the brakes on STRIDER, an international placebo-controlled study looking at sildenafil as a treatment for early-onset intrauterine growth restriction (IUGR).

stockce/Thinkstock

The study’s independent data safety monitoring board halted STRIDER (Sildenafil Therapy in Dismal Prognosis Early-Onset Fetal Growth Restriction) last July, after an interim safety analysis identified possible fetal harm and no signal of benefit over placebo, Dr. Anouk Pels reported at the annual meeting of the Society for Maternal-Fetal Medicine. The late-breaking presentation at the meeting revealed the first outcome data details.

The board had “serious concerns that sildenafil may cause harm to newborn children. … Given the results , it is extremely unlikely that any benefit could be shown on the primary endpoint if the trial is continued to its completion,” said Dr. Pels of the University of Amsterdam. “Our recommendation is not to use sildenafil for this indication in pregnant women.”

Although the link remains as-yet unproven, pulmonary hypertension among sildenafil-exposed neonates is biologically plausible, she said. It could have been a symptomatic rebound response to the discontinuation of constant intrauterine sildenafil exposure – or it could have been a hint of something more profound. Like the genital vasculature, pulmonary vasculature is a target of the drug. Intrauterine exposure to sildenafil could theoretically alter its development.

“It’s possible that sildenafil may be causing structural changes in the pulmonary vasculature of fetuses. This needs to be explored further, and we will do so by performing additional analyses on autopsy data and placental histology.”

STRIDER involved 261 pregnant women diagnosed with severe early-onset fetal growth restriction. They were randomized to sildenafil 25 mg or placebo three times daily until delivery or 32 weeks’ gestation. A safety analysis was conducted after every 50 patients were enrolled. The preplanned interim analysis was conducted after half of the cohort had been enrolled and received at least one dose of the study medication.

The primary outcome was a composite measure of neonatal mortality or major neonatal morbidity at hospital discharge.

Gestational age at baseline was about 24.6 weeks, and the estimated fetal weight by ultrasound, 465 g. About 45% of pregnancies had evidence of a notching in the uterine artery. In about 42%, the pulsatility index of the umbilical artery was above the 95th percentile; the pulsatility index of the middle cerebral artery was below the 5% percentile in about 70% of cases.

About a quarter of the women had a diagnosis of pregnancy-induced hypertension, and another quarter, preeclampsia. Women used the study medication for a mean of 22 days.

There were no significant between-group differences in maternal outcomes. Median gestational age at delivery was 28 weeks in both groups. About 10% in each group experienced new-onset pregnancy-induced hypertension; About a quarter of each group developed new-onset preeclampsia or HELLP (hemolysis, elevated liver enzymes, low platelet count). There were no between-group differences in the number of maternal antihypertensives prescribed.

The primary combined outcome of neonatal mortality or major neonatal morbidity occurred in 66 of the sildenafil-exposed neonates and 58 of the placebo-exposed infants (61% vs. 54%) – not a significant difference. Fetal death occurred in 23 and 29 pregnancies, respectively (21% and 27%); neonatal death occurred in 21 and 11, respectively (19% and 10%). Overall, fetal/neonatal mortality was similar between the sildenafil and placebo groups (41% and 37%, respectively).

Of the 64 sildenafil-exposed neonates who survived to hospital discharge, 22 exhibited clinically relevant morbidity. Of the 67 in the placebo-treated group who survived to hospital discharge, 18 had clinically relevant morbidity. Overall, 42 in the sildenafil group and 49 of the placebo group survived to hospital discharge without relevant morbidity.

There were a number of secondary outcomes, none exhibiting any significant between-group differences. These included the median weights of those who experienced intrauterine death (425 g and 350 g), median live birth weight (725 g and 783 g), intraventricular hemorrhage of grade II or IV (3% and 2%), periventricular hemorrhage grade II or higher (0%, both groups), necrotizing enterocolitis grade II or higher (7% and 8%), and at least one culture-proven or clinical infection (41% and 33%).

The significantly higher rates of pulmonary hypertension in the sildenafil-exposed neonates was the showstopper. Almost half of the 21 who died had proven pulmonary hypertension (10), as did 6 of the 64 who survived – an excess of 16 cases. Of proven cases, 11 were persistent pulmonary hypertension. There were also two cases of sepsis-associated pulmonary hypertension and four cases of bronchopulmonary dysplasia associated with the disorder. In the placebo-exposed group, pulmonary hypertension occurred in 3 of the 11 deaths and 1 of the 67 who survived. Of proven cases, two were persistent pulmonary hypertension. There was no sepsis-associated pulmonary hypertension, but there were three cases of bronchopulmonary dysplasia associated with the disorder. Some children had both persistent pulmonary hypertension and bronchopulmonary dysplasia.

“While there was no difference in the primary outcomes or in overall mortality, there were more cases of pulmonary hypertension in the sildenafil group,” Dr. Pels said. “We can speculate on the cause, whether it was related to sildenafil and why, or whether it was simply chance. This is the reason we need to conduct more in-depth analyses of these data.”

Funding came from federal health agencies and universities in the countries where STRIDER was conducted, including New Zealand, Australia, the United Kingdom, Ireland, and the Netherlands. Dr. Pels had no relevant financial disclosures.

SOURCE: Pels A et al. The Pregnancy Meeting, Late-Breaker 2.

LAS VEGAS – Increased rates of persistent neonatal pulmonary hypertension in neonates put the brakes on STRIDER, an international placebo-controlled study looking at sildenafil as a treatment for early-onset intrauterine growth restriction (IUGR).

stockce/Thinkstock

The study’s independent data safety monitoring board halted STRIDER (Sildenafil Therapy in Dismal Prognosis Early-Onset Fetal Growth Restriction) last July, after an interim safety analysis identified possible fetal harm and no signal of benefit over placebo, Dr. Anouk Pels reported at the annual meeting of the Society for Maternal-Fetal Medicine. The late-breaking presentation at the meeting revealed the first outcome data details.

The board had “serious concerns that sildenafil may cause harm to newborn children. … Given the results , it is extremely unlikely that any benefit could be shown on the primary endpoint if the trial is continued to its completion,” said Dr. Pels of the University of Amsterdam. “Our recommendation is not to use sildenafil for this indication in pregnant women.”

Although the link remains as-yet unproven, pulmonary hypertension among sildenafil-exposed neonates is biologically plausible, she said. It could have been a symptomatic rebound response to the discontinuation of constant intrauterine sildenafil exposure – or it could have been a hint of something more profound. Like the genital vasculature, pulmonary vasculature is a target of the drug. Intrauterine exposure to sildenafil could theoretically alter its development.

“It’s possible that sildenafil may be causing structural changes in the pulmonary vasculature of fetuses. This needs to be explored further, and we will do so by performing additional analyses on autopsy data and placental histology.”

STRIDER involved 261 pregnant women diagnosed with severe early-onset fetal growth restriction. They were randomized to sildenafil 25 mg or placebo three times daily until delivery or 32 weeks’ gestation. A safety analysis was conducted after every 50 patients were enrolled. The preplanned interim analysis was conducted after half of the cohort had been enrolled and received at least one dose of the study medication.

The primary outcome was a composite measure of neonatal mortality or major neonatal morbidity at hospital discharge.

Gestational age at baseline was about 24.6 weeks, and the estimated fetal weight by ultrasound, 465 g. About 45% of pregnancies had evidence of a notching in the uterine artery. In about 42%, the pulsatility index of the umbilical artery was above the 95th percentile; the pulsatility index of the middle cerebral artery was below the 5% percentile in about 70% of cases.

About a quarter of the women had a diagnosis of pregnancy-induced hypertension, and another quarter, preeclampsia. Women used the study medication for a mean of 22 days.

There were no significant between-group differences in maternal outcomes. Median gestational age at delivery was 28 weeks in both groups. About 10% in each group experienced new-onset pregnancy-induced hypertension; About a quarter of each group developed new-onset preeclampsia or HELLP (hemolysis, elevated liver enzymes, low platelet count). There were no between-group differences in the number of maternal antihypertensives prescribed.

The primary combined outcome of neonatal mortality or major neonatal morbidity occurred in 66 of the sildenafil-exposed neonates and 58 of the placebo-exposed infants (61% vs. 54%) – not a significant difference. Fetal death occurred in 23 and 29 pregnancies, respectively (21% and 27%); neonatal death occurred in 21 and 11, respectively (19% and 10%). Overall, fetal/neonatal mortality was similar between the sildenafil and placebo groups (41% and 37%, respectively).

Of the 64 sildenafil-exposed neonates who survived to hospital discharge, 22 exhibited clinically relevant morbidity. Of the 67 in the placebo-treated group who survived to hospital discharge, 18 had clinically relevant morbidity. Overall, 42 in the sildenafil group and 49 of the placebo group survived to hospital discharge without relevant morbidity.

There were a number of secondary outcomes, none exhibiting any significant between-group differences. These included the median weights of those who experienced intrauterine death (425 g and 350 g), median live birth weight (725 g and 783 g), intraventricular hemorrhage of grade II or IV (3% and 2%), periventricular hemorrhage grade II or higher (0%, both groups), necrotizing enterocolitis grade II or higher (7% and 8%), and at least one culture-proven or clinical infection (41% and 33%).

The significantly higher rates of pulmonary hypertension in the sildenafil-exposed neonates was the showstopper. Almost half of the 21 who died had proven pulmonary hypertension (10), as did 6 of the 64 who survived – an excess of 16 cases. Of proven cases, 11 were persistent pulmonary hypertension. There were also two cases of sepsis-associated pulmonary hypertension and four cases of bronchopulmonary dysplasia associated with the disorder. In the placebo-exposed group, pulmonary hypertension occurred in 3 of the 11 deaths and 1 of the 67 who survived. Of proven cases, two were persistent pulmonary hypertension. There was no sepsis-associated pulmonary hypertension, but there were three cases of bronchopulmonary dysplasia associated with the disorder. Some children had both persistent pulmonary hypertension and bronchopulmonary dysplasia.

“While there was no difference in the primary outcomes or in overall mortality, there were more cases of pulmonary hypertension in the sildenafil group,” Dr. Pels said. “We can speculate on the cause, whether it was related to sildenafil and why, or whether it was simply chance. This is the reason we need to conduct more in-depth analyses of these data.”

Funding came from federal health agencies and universities in the countries where STRIDER was conducted, including New Zealand, Australia, the United Kingdom, Ireland, and the Netherlands. Dr. Pels had no relevant financial disclosures.

SOURCE: Pels A et al. The Pregnancy Meeting, Late-Breaker 2.

Two years ago, a now 45-year-old woman was diagnosed with asthma based on her history and physical exam findings; she was prescribed an inhaled corticosteroid and a bronchodilator rescue inhaler. She has had no exacerbations since. Should you consider weaning her off the inhalers?

Asthma is a prevalent problem; 8% of adults ages 18 to 64 have the chronic lung disease.² Diagnosis can be challenging, partially because it requires measurement of transient airway resistance, and treatment entails significant costs and possible adverse effects. Without pulmonary function measurement or trials off medication, there is no clinical way to differentiate patients with well-controlled asthma from those who are being treated unnecessarily. Not surprisingly, studies have shown that ruling out active asthma and reducing medication use are cost effective.^3,4 This study followed a cohort of patients to see how many could be weaned off their asthma medications.

STUDY SUMMARY

About one-third of adults with asthma are “undiagnosed” within 5 years

The researchers recruited participants from the general population of the 10 largest cities and surrounding areas in Canada by randomly dialing cellular and landline phone numbers and asking about adult household members with asthma.¹ The researchers focused on those with a recent (<5 years) asthma diagnosis to represent contemporary diagnostic practice and make it easier to collect medical records. Participants lived within 90 minutes of 10 medical centers. Patients were excluded if they were using long-term oral steroids, were pregnant or breastfeeding, were unable to tolerate spirometry or methacholine challenges, or had a smoking history of >10 pack-years.

Of the 701 patients enrolled, 613 (87.4%) completed all study assessments. Patients progressed through a series of spirometry tests and were then tapered off their asthma-controlling medications.

The initial spirometry test confirmed asthma if bronchodilators caused a significant improvement in forced expiratory volume in one second (FEV₁). Patients who showed no improvement took a methacholine challenge 1 week later; if they did well, their maintenance medications were reduced by half. About 1 month later, another methacholine challenge was given; if the patient did well, maintenance medications were stopped and the patient underwent a third methacholine challenge 3 weeks later.

Asthma was confirmed at any methacholine challenge if there was a 20% decrease in FEV₁ from baseline at a methacholine concentration of ≤8 mg/mL; these patients were restarted on appropriate medications. If current asthma was ruled out, follow-up bronchial challenges were repeated at 6 and 12 months.

Results. Among the patients with clinician-diagnosed asthma, 33.1% no longer met criteria for an asthma diagnosis. Of those who no longer had asthma, 44% had previously undergone objective testing of airflow limitation. Another 12 patients (2%) had other serious cardiorespiratory conditions instead of asthma (eg, ischemic heart disease, subglottic stenosis, and bronchiectasis).

Continue to: During the 1-year follow-up period...

During the 1-year follow-up period, 22 (10.8%) of the 203 patients who were initially judged to no longer have asthma had a positive bronchial challenge test; 16 had no symptoms and continued to do well without any asthma medications. Six (3%) presented with respiratory symptoms and resumed treatment with asthma medications, but only 1 (0.5%) required oral corticosteroid therapy.

WHAT’S NEW?

Asthma meds of no benefit for one-third of patients taking them

This study found that one-third of patients with asthma diagnosed in the past 5 years no longer had symptoms or spirometry results consistent with asthma and did well in the subsequent year. For those patients, asthma medications appear to have no benefit. The Global Institute for Asthma recommends stepping down treatment in adults with asthma that is well controlled for 3 months or more.⁵ Patients with objectively confirmed asthma diagnoses were more likely to still have asthma in this study—but more than 40% of patients who no longer had asthma had been objectively proven to have the disease at the time of diagnosis.

CAVEATS

High level of rigor; no randomized trial

This study used a very structured protocol for tapering patients off their medications, including multiple spirometry tests (most including methacholine challenges) and oversight by pulmonologists. It is unclear whether this level of rigor is necessary for weaning in other clinical settings.

Also, this study was not a randomized trial, which is the gold standard for withdrawal of therapy. However, a cohort study is adequate to assess diagnostic testing, and this could be considered a trial of “undiagnosing” asthma in adults. These results are consistent with those of another study of asthma disappearance in patients with and without obesity; in that study, about 30% of patients in either group no longer had a diagnosis of asthma.⁶

Using random dialing is likely to have broadened the pool of patients this study drew upon. Also, there is a possibility that the patients who were lost to follow-up in this study represented those who had worsening symptoms. Some patients with mild asthma may have a waxing and waning course; it is possible that the study period was not long enough to capture this. In this study, only about 3% of patients who had their medications stopped reported worsening of symptoms.

Continue to: CHALLENGES TO IMPLEMENTATION

“Undiagnosis” is unusual

Using objective testing may provide some logistical or financial challenges for patients. Furthermore, “undiagnosing” a chronic disease like asthma is not a clinician’s typical work, and it may take some time and effort to educate and monitor patients throughout the process.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[11]:704,706-707).

Two years ago, a now 45-year-old woman was diagnosed with asthma based on her history and physical exam findings; she was prescribed an inhaled corticosteroid and a bronchodilator rescue inhaler. She has had no exacerbations since. Should you consider weaning her off the inhalers?

Asthma is a prevalent problem; 8% of adults ages 18 to 64 have the chronic lung disease.² Diagnosis can be challenging, partially because it requires measurement of transient airway resistance, and treatment entails significant costs and possible adverse effects. Without pulmonary function measurement or trials off medication, there is no clinical way to differentiate patients with well-controlled asthma from those who are being treated unnecessarily. Not surprisingly, studies have shown that ruling out active asthma and reducing medication use are cost effective.^3,4 This study followed a cohort of patients to see how many could be weaned off their asthma medications.

STUDY SUMMARY

About one-third of adults with asthma are “undiagnosed” within 5 years

The researchers recruited participants from the general population of the 10 largest cities and surrounding areas in Canada by randomly dialing cellular and landline phone numbers and asking about adult household members with asthma.¹ The researchers focused on those with a recent (<5 years) asthma diagnosis to represent contemporary diagnostic practice and make it easier to collect medical records. Participants lived within 90 minutes of 10 medical centers. Patients were excluded if they were using long-term oral steroids, were pregnant or breastfeeding, were unable to tolerate spirometry or methacholine challenges, or had a smoking history of >10 pack-years.

Of the 701 patients enrolled, 613 (87.4%) completed all study assessments. Patients progressed through a series of spirometry tests and were then tapered off their asthma-controlling medications.

The initial spirometry test confirmed asthma if bronchodilators caused a significant improvement in forced expiratory volume in one second (FEV₁). Patients who showed no improvement took a methacholine challenge 1 week later; if they did well, their maintenance medications were reduced by half. About 1 month later, another methacholine challenge was given; if the patient did well, maintenance medications were stopped and the patient underwent a third methacholine challenge 3 weeks later.

Asthma was confirmed at any methacholine challenge if there was a 20% decrease in FEV₁ from baseline at a methacholine concentration of ≤8 mg/mL; these patients were restarted on appropriate medications. If current asthma was ruled out, follow-up bronchial challenges were repeated at 6 and 12 months.

Results. Among the patients with clinician-diagnosed asthma, 33.1% no longer met criteria for an asthma diagnosis. Of those who no longer had asthma, 44% had previously undergone objective testing of airflow limitation. Another 12 patients (2%) had other serious cardiorespiratory conditions instead of asthma (eg, ischemic heart disease, subglottic stenosis, and bronchiectasis).

Continue to: During the 1-year follow-up period...

During the 1-year follow-up period, 22 (10.8%) of the 203 patients who were initially judged to no longer have asthma had a positive bronchial challenge test; 16 had no symptoms and continued to do well without any asthma medications. Six (3%) presented with respiratory symptoms and resumed treatment with asthma medications, but only 1 (0.5%) required oral corticosteroid therapy.

WHAT’S NEW?

Asthma meds of no benefit for one-third of patients taking them

This study found that one-third of patients with asthma diagnosed in the past 5 years no longer had symptoms or spirometry results consistent with asthma and did well in the subsequent year. For those patients, asthma medications appear to have no benefit. The Global Institute for Asthma recommends stepping down treatment in adults with asthma that is well controlled for 3 months or more.⁵ Patients with objectively confirmed asthma diagnoses were more likely to still have asthma in this study—but more than 40% of patients who no longer had asthma had been objectively proven to have the disease at the time of diagnosis.

CAVEATS

High level of rigor; no randomized trial

This study used a very structured protocol for tapering patients off their medications, including multiple spirometry tests (most including methacholine challenges) and oversight by pulmonologists. It is unclear whether this level of rigor is necessary for weaning in other clinical settings.

Also, this study was not a randomized trial, which is the gold standard for withdrawal of therapy. However, a cohort study is adequate to assess diagnostic testing, and this could be considered a trial of “undiagnosing” asthma in adults. These results are consistent with those of another study of asthma disappearance in patients with and without obesity; in that study, about 30% of patients in either group no longer had a diagnosis of asthma.⁶

Using random dialing is likely to have broadened the pool of patients this study drew upon. Also, there is a possibility that the patients who were lost to follow-up in this study represented those who had worsening symptoms. Some patients with mild asthma may have a waxing and waning course; it is possible that the study period was not long enough to capture this. In this study, only about 3% of patients who had their medications stopped reported worsening of symptoms.

Continue to: CHALLENGES TO IMPLEMENTATION

“Undiagnosis” is unusual

Using objective testing may provide some logistical or financial challenges for patients. Furthermore, “undiagnosing” a chronic disease like asthma is not a clinician’s typical work, and it may take some time and effort to educate and monitor patients throughout the process.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[11]:704,706-707).

Two years ago, a now 45-year-old woman was diagnosed with asthma based on her history and physical exam findings; she was prescribed an inhaled corticosteroid and a bronchodilator rescue inhaler. She has had no exacerbations since. Should you consider weaning her off the inhalers?

Asthma is a prevalent problem; 8% of adults ages 18 to 64 have the chronic lung disease.² Diagnosis can be challenging, partially because it requires measurement of transient airway resistance, and treatment entails significant costs and possible adverse effects. Without pulmonary function measurement or trials off medication, there is no clinical way to differentiate patients with well-controlled asthma from those who are being treated unnecessarily. Not surprisingly, studies have shown that ruling out active asthma and reducing medication use are cost effective.^3,4 This study followed a cohort of patients to see how many could be weaned off their asthma medications.

STUDY SUMMARY

About one-third of adults with asthma are “undiagnosed” within 5 years

The researchers recruited participants from the general population of the 10 largest cities and surrounding areas in Canada by randomly dialing cellular and landline phone numbers and asking about adult household members with asthma.¹ The researchers focused on those with a recent (<5 years) asthma diagnosis to represent contemporary diagnostic practice and make it easier to collect medical records. Participants lived within 90 minutes of 10 medical centers. Patients were excluded if they were using long-term oral steroids, were pregnant or breastfeeding, were unable to tolerate spirometry or methacholine challenges, or had a smoking history of >10 pack-years.

Of the 701 patients enrolled, 613 (87.4%) completed all study assessments. Patients progressed through a series of spirometry tests and were then tapered off their asthma-controlling medications.

The initial spirometry test confirmed asthma if bronchodilators caused a significant improvement in forced expiratory volume in one second (FEV₁). Patients who showed no improvement took a methacholine challenge 1 week later; if they did well, their maintenance medications were reduced by half. About 1 month later, another methacholine challenge was given; if the patient did well, maintenance medications were stopped and the patient underwent a third methacholine challenge 3 weeks later.

Asthma was confirmed at any methacholine challenge if there was a 20% decrease in FEV₁ from baseline at a methacholine concentration of ≤8 mg/mL; these patients were restarted on appropriate medications. If current asthma was ruled out, follow-up bronchial challenges were repeated at 6 and 12 months.

Results. Among the patients with clinician-diagnosed asthma, 33.1% no longer met criteria for an asthma diagnosis. Of those who no longer had asthma, 44% had previously undergone objective testing of airflow limitation. Another 12 patients (2%) had other serious cardiorespiratory conditions instead of asthma (eg, ischemic heart disease, subglottic stenosis, and bronchiectasis).

Continue to: During the 1-year follow-up period...

During the 1-year follow-up period, 22 (10.8%) of the 203 patients who were initially judged to no longer have asthma had a positive bronchial challenge test; 16 had no symptoms and continued to do well without any asthma medications. Six (3%) presented with respiratory symptoms and resumed treatment with asthma medications, but only 1 (0.5%) required oral corticosteroid therapy.

WHAT’S NEW?

Asthma meds of no benefit for one-third of patients taking them

This study found that one-third of patients with asthma diagnosed in the past 5 years no longer had symptoms or spirometry results consistent with asthma and did well in the subsequent year. For those patients, asthma medications appear to have no benefit. The Global Institute for Asthma recommends stepping down treatment in adults with asthma that is well controlled for 3 months or more.⁵ Patients with objectively confirmed asthma diagnoses were more likely to still have asthma in this study—but more than 40% of patients who no longer had asthma had been objectively proven to have the disease at the time of diagnosis.

CAVEATS

High level of rigor; no randomized trial

This study used a very structured protocol for tapering patients off their medications, including multiple spirometry tests (most including methacholine challenges) and oversight by pulmonologists. It is unclear whether this level of rigor is necessary for weaning in other clinical settings.

Also, this study was not a randomized trial, which is the gold standard for withdrawal of therapy. However, a cohort study is adequate to assess diagnostic testing, and this could be considered a trial of “undiagnosing” asthma in adults. These results are consistent with those of another study of asthma disappearance in patients with and without obesity; in that study, about 30% of patients in either group no longer had a diagnosis of asthma.⁶

Using random dialing is likely to have broadened the pool of patients this study drew upon. Also, there is a possibility that the patients who were lost to follow-up in this study represented those who had worsening symptoms. Some patients with mild asthma may have a waxing and waning course; it is possible that the study period was not long enough to capture this. In this study, only about 3% of patients who had their medications stopped reported worsening of symptoms.

Continue to: CHALLENGES TO IMPLEMENTATION

“Undiagnosis” is unusual

Using objective testing may provide some logistical or financial challenges for patients. Furthermore, “undiagnosing” a chronic disease like asthma is not a clinician’s typical work, and it may take some time and effort to educate and monitor patients throughout the process.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018; 67[11]:704,706-707).

WAIKOLOA, HAWAII – The Caribbean islands and Central and South America are among the most popular travel destinations for Americans. And some of these visitors will come home harboring unwelcome guests: Infestations that will eventually bring them to a dermatologist’s attention.

Bruce Jancin/MDedge News

“I always tell the residents that if a patient’s country of travel starts with a B – Barbados, Belize, Bolivia, Brazil – it’s going to be something fun,” Natasha A. Mesinkovska, MD, PhD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

According to surveillance conducted by the Centers for Disease Control and Prevention and the International Society for Travel Medicine, the four most common tropical skin infestations brought back by U.S. travelers within the Americas are cutaneous larva migrans, myiasis, tungiasis, and leishmaniasis.

Cutaneous larva migrans is the easiest to diagnosis because it’s a creeping eruption that often migrates at a rate of 1-2 cm per day. Patients with the other disorders often present with a complaint of a common skin condition – described as a pimple, a wart, a patch of sunburn – that just doesn’t go away, according to Dr. Mesinkovska, director of clinical research in the department of dermatology at the University of California, Irvine.

Tungiasis

Tungiasis is caused by the female sand flea, Tunga penetrans, which burrows into the skin, where it lays hundreds of eggs within a matter of a few days. The sand flea is harbored by dogs, cats, pigs, cows, and rats. It’s rare to encounter tungiasis in travelers who’ve spent their time in fancy resorts, ecolodges, or yoga retreats, even if they’ve been parading around with lots of exposed skin. This is a disease of impoverished neighborhoods; hence, affected Americans often have been doing mission work abroad. In tropical areas, tungiasis is a debilitating, mutilating disorder marked by repeated infections, persistent inflammation, fissures, and ulcers.

Treatment involves a topical antiparasitic agent such as ivermectin, metrifonate, or thiabendazole and removal of the flea with sterile forceps or needles. But there is a promising new treatment concept: topical dimethicone, or polydimethylsiloxane. Studies have shown that following application of dimethicone, roughly 80%-90% of sand fleas are dead within 7 days.

“It’s nontoxic and has a purely physical mechanism of action, so resistance is unlikely ... I think it’s going to change the way this condition gets controlled,” Dr. Mesinkovska said.

Myiasis

The differential diagnosis of myiasis includes impetigo, a furuncle, an infected cyst, or a retained foreign body. Myiasis is a cutaneous infestation of the larva of certain flies, among the most notorious of which are the botfly, blowfly, and screwfly. The female fly lays her eggs in hot, humid, shady areas in soil contaminated by feces or urine. The larva can invade unbroken skin instantaneously and painlessly. Then it begins burrowing in. An air hole is always present in the skin so the organism can breathe. Ophthalmomyiasis is common, as are nasal and aural infections, the latter often accompanied by complaints of a crawling sensation inside the ear along with a buzzing noise. To avoid infection, in endemic areas it’s important not to go barefoot or to dry clothes on bushes or on the ground. Treatment entails elimination of the larva. Covering the air hole with petroleum jelly will force it to the surface. There is just one larva per furuncle, so no need for further extensive exploration once that critter has been extracted.

Leishmaniasis

The vector for this protozoan infection is the sandfly, which feeds from dusk to dawn noiselessly and painlessly. Because cutaneous and mucocutaneous leishmaniasis are understudied orphan diseases for which current treatments are less than satisfactory, prevention is the watchword. In endemic areas it’s important to close the windows and make use of air conditioning and ceiling fans when available. When in doubt, it’s advisable to sleep using a bed net treated with permethrin.

Cutaneous larva migrans

Courtesy Mark Ash, Brody School of Medicine, Greenville, N.C., and Dr. Donna Bilu Martin, Premier Dermatology MD, Aventura, Fla.

This skin eruption is caused by parasitic hookworms, the most common of which in the Americas is Ancylostoma braziliense. The eggs are transmitted through dog and cat feces deposited on soil or sand.

“Avoid laying or sitting on dry sand, even on a towel. And wear shoes,” Dr. Mesinkovska advised.

Among the CDC’s treatment recommendations for cutaneous larva migrans are several agents with poor efficacy and/or considerable side effects. But there is one standout therapy.

“Really, I would say nowadays the easiest thing is one 12-mg oral dose of ivermectin. It’s almost 100% effective,” she said.

Dr. Mesinkovska reported having no financial interests relevant to her talk.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – The Caribbean islands and Central and South America are among the most popular travel destinations for Americans. And some of these visitors will come home harboring unwelcome guests: Infestations that will eventually bring them to a dermatologist’s attention.

Bruce Jancin/MDedge News

“I always tell the residents that if a patient’s country of travel starts with a B – Barbados, Belize, Bolivia, Brazil – it’s going to be something fun,” Natasha A. Mesinkovska, MD, PhD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

According to surveillance conducted by the Centers for Disease Control and Prevention and the International Society for Travel Medicine, the four most common tropical skin infestations brought back by U.S. travelers within the Americas are cutaneous larva migrans, myiasis, tungiasis, and leishmaniasis.

Cutaneous larva migrans is the easiest to diagnosis because it’s a creeping eruption that often migrates at a rate of 1-2 cm per day. Patients with the other disorders often present with a complaint of a common skin condition – described as a pimple, a wart, a patch of sunburn – that just doesn’t go away, according to Dr. Mesinkovska, director of clinical research in the department of dermatology at the University of California, Irvine.

Tungiasis

Tungiasis is caused by the female sand flea, Tunga penetrans, which burrows into the skin, where it lays hundreds of eggs within a matter of a few days. The sand flea is harbored by dogs, cats, pigs, cows, and rats. It’s rare to encounter tungiasis in travelers who’ve spent their time in fancy resorts, ecolodges, or yoga retreats, even if they’ve been parading around with lots of exposed skin. This is a disease of impoverished neighborhoods; hence, affected Americans often have been doing mission work abroad. In tropical areas, tungiasis is a debilitating, mutilating disorder marked by repeated infections, persistent inflammation, fissures, and ulcers.

Treatment involves a topical antiparasitic agent such as ivermectin, metrifonate, or thiabendazole and removal of the flea with sterile forceps or needles. But there is a promising new treatment concept: topical dimethicone, or polydimethylsiloxane. Studies have shown that following application of dimethicone, roughly 80%-90% of sand fleas are dead within 7 days.

“It’s nontoxic and has a purely physical mechanism of action, so resistance is unlikely ... I think it’s going to change the way this condition gets controlled,” Dr. Mesinkovska said.

Myiasis

The differential diagnosis of myiasis includes impetigo, a furuncle, an infected cyst, or a retained foreign body. Myiasis is a cutaneous infestation of the larva of certain flies, among the most notorious of which are the botfly, blowfly, and screwfly. The female fly lays her eggs in hot, humid, shady areas in soil contaminated by feces or urine. The larva can invade unbroken skin instantaneously and painlessly. Then it begins burrowing in. An air hole is always present in the skin so the organism can breathe. Ophthalmomyiasis is common, as are nasal and aural infections, the latter often accompanied by complaints of a crawling sensation inside the ear along with a buzzing noise. To avoid infection, in endemic areas it’s important not to go barefoot or to dry clothes on bushes or on the ground. Treatment entails elimination of the larva. Covering the air hole with petroleum jelly will force it to the surface. There is just one larva per furuncle, so no need for further extensive exploration once that critter has been extracted.

Leishmaniasis

The vector for this protozoan infection is the sandfly, which feeds from dusk to dawn noiselessly and painlessly. Because cutaneous and mucocutaneous leishmaniasis are understudied orphan diseases for which current treatments are less than satisfactory, prevention is the watchword. In endemic areas it’s important to close the windows and make use of air conditioning and ceiling fans when available. When in doubt, it’s advisable to sleep using a bed net treated with permethrin.

Cutaneous larva migrans

Courtesy Mark Ash, Brody School of Medicine, Greenville, N.C., and Dr. Donna Bilu Martin, Premier Dermatology MD, Aventura, Fla.

This skin eruption is caused by parasitic hookworms, the most common of which in the Americas is Ancylostoma braziliense. The eggs are transmitted through dog and cat feces deposited on soil or sand.

“Avoid laying or sitting on dry sand, even on a towel. And wear shoes,” Dr. Mesinkovska advised.

Among the CDC’s treatment recommendations for cutaneous larva migrans are several agents with poor efficacy and/or considerable side effects. But there is one standout therapy.

“Really, I would say nowadays the easiest thing is one 12-mg oral dose of ivermectin. It’s almost 100% effective,” she said.

Dr. Mesinkovska reported having no financial interests relevant to her talk.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – The Caribbean islands and Central and South America are among the most popular travel destinations for Americans. And some of these visitors will come home harboring unwelcome guests: Infestations that will eventually bring them to a dermatologist’s attention.

Bruce Jancin/MDedge News

“I always tell the residents that if a patient’s country of travel starts with a B – Barbados, Belize, Bolivia, Brazil – it’s going to be something fun,” Natasha A. Mesinkovska, MD, PhD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

According to surveillance conducted by the Centers for Disease Control and Prevention and the International Society for Travel Medicine, the four most common tropical skin infestations brought back by U.S. travelers within the Americas are cutaneous larva migrans, myiasis, tungiasis, and leishmaniasis.

Cutaneous larva migrans is the easiest to diagnosis because it’s a creeping eruption that often migrates at a rate of 1-2 cm per day. Patients with the other disorders often present with a complaint of a common skin condition – described as a pimple, a wart, a patch of sunburn – that just doesn’t go away, according to Dr. Mesinkovska, director of clinical research in the department of dermatology at the University of California, Irvine.

Tungiasis

Tungiasis is caused by the female sand flea, Tunga penetrans, which burrows into the skin, where it lays hundreds of eggs within a matter of a few days. The sand flea is harbored by dogs, cats, pigs, cows, and rats. It’s rare to encounter tungiasis in travelers who’ve spent their time in fancy resorts, ecolodges, or yoga retreats, even if they’ve been parading around with lots of exposed skin. This is a disease of impoverished neighborhoods; hence, affected Americans often have been doing mission work abroad. In tropical areas, tungiasis is a debilitating, mutilating disorder marked by repeated infections, persistent inflammation, fissures, and ulcers.

Treatment involves a topical antiparasitic agent such as ivermectin, metrifonate, or thiabendazole and removal of the flea with sterile forceps or needles. But there is a promising new treatment concept: topical dimethicone, or polydimethylsiloxane. Studies have shown that following application of dimethicone, roughly 80%-90% of sand fleas are dead within 7 days.

“It’s nontoxic and has a purely physical mechanism of action, so resistance is unlikely ... I think it’s going to change the way this condition gets controlled,” Dr. Mesinkovska said.

Myiasis

The differential diagnosis of myiasis includes impetigo, a furuncle, an infected cyst, or a retained foreign body. Myiasis is a cutaneous infestation of the larva of certain flies, among the most notorious of which are the botfly, blowfly, and screwfly. The female fly lays her eggs in hot, humid, shady areas in soil contaminated by feces or urine. The larva can invade unbroken skin instantaneously and painlessly. Then it begins burrowing in. An air hole is always present in the skin so the organism can breathe. Ophthalmomyiasis is common, as are nasal and aural infections, the latter often accompanied by complaints of a crawling sensation inside the ear along with a buzzing noise. To avoid infection, in endemic areas it’s important not to go barefoot or to dry clothes on bushes or on the ground. Treatment entails elimination of the larva. Covering the air hole with petroleum jelly will force it to the surface. There is just one larva per furuncle, so no need for further extensive exploration once that critter has been extracted.

Leishmaniasis

The vector for this protozoan infection is the sandfly, which feeds from dusk to dawn noiselessly and painlessly. Because cutaneous and mucocutaneous leishmaniasis are understudied orphan diseases for which current treatments are less than satisfactory, prevention is the watchword. In endemic areas it’s important to close the windows and make use of air conditioning and ceiling fans when available. When in doubt, it’s advisable to sleep using a bed net treated with permethrin.

Cutaneous larva migrans

Courtesy Mark Ash, Brody School of Medicine, Greenville, N.C., and Dr. Donna Bilu Martin, Premier Dermatology MD, Aventura, Fla.

This skin eruption is caused by parasitic hookworms, the most common of which in the Americas is Ancylostoma braziliense. The eggs are transmitted through dog and cat feces deposited on soil or sand.

“Avoid laying or sitting on dry sand, even on a towel. And wear shoes,” Dr. Mesinkovska advised.

Among the CDC’s treatment recommendations for cutaneous larva migrans are several agents with poor efficacy and/or considerable side effects. But there is one standout therapy.

“Really, I would say nowadays the easiest thing is one 12-mg oral dose of ivermectin. It’s almost 100% effective,” she said.

Dr. Mesinkovska reported having no financial interests relevant to her talk.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

More than one-third of hepatitis C virus-infected patients in the emergency department (ED) were found to have advanced liver fibrosis and higher mortality, according to the results of a retrospective study of 113 known patients with HCV at a single institution.

Courtesy NIH

As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were retrospectively identified. Components of FIB-4 (a noninvasive serum fibrosis index, which includes age, alanine aminotransferase, aspartate aminotransferase, and platelet count), were abstracted. Patients with an FIB-4 greater than 3.25 were classified with advanced fibrosis and characterized with regard to downstream outcomes at 1 year after enrollment.

The 1-year outcomes after the ED encounter for the 113 patients showed 38 with and 75 patients without advanced fibrosis. Among these, 72 (96%) and 34 (89.5%), respectively, agreed to be linked to HCV care. Ten patients of the total number of patients died within the 1-year follow-up. For those HCV-infected patients with advanced liver fibrosis compared to those without, all-cause mortality was more than fourfold higher, (18.4% [7 patients] vs. 4.0% [3 patients], P = .030), according to Yu-Hsiang Hsieh, PhD, associate professor of emergency medicine at Johns Hopkins University, Baltimore, and his colleagues (Am J Emerg Med. 2019;37[2]:286-90).

“Given the substantial burden of HCV-related illness in urban ED patients nationally, and the recognized fact that EDs are often the only point of contact with the health care system for many of these patients, we propose incorporating FIB-4 based rapid assessment into ED-based HCV screening and LTC programs in order to prioritize LTC for patients with advanced liver fibrosis, as well as routine ED clinical practice,” the researchers concluded.

They reported having no conflicts.

[email protected]

SOURCE: Yu-Hsiang Hsieh Y-H, Am J Emerg Med. 2019;37[2]:286-90.

More than one-third of hepatitis C virus-infected patients in the emergency department (ED) were found to have advanced liver fibrosis and higher mortality, according to the results of a retrospective study of 113 known patients with HCV at a single institution.

Courtesy NIH

As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were retrospectively identified. Components of FIB-4 (a noninvasive serum fibrosis index, which includes age, alanine aminotransferase, aspartate aminotransferase, and platelet count), were abstracted. Patients with an FIB-4 greater than 3.25 were classified with advanced fibrosis and characterized with regard to downstream outcomes at 1 year after enrollment.

The 1-year outcomes after the ED encounter for the 113 patients showed 38 with and 75 patients without advanced fibrosis. Among these, 72 (96%) and 34 (89.5%), respectively, agreed to be linked to HCV care. Ten patients of the total number of patients died within the 1-year follow-up. For those HCV-infected patients with advanced liver fibrosis compared to those without, all-cause mortality was more than fourfold higher, (18.4% [7 patients] vs. 4.0% [3 patients], P = .030), according to Yu-Hsiang Hsieh, PhD, associate professor of emergency medicine at Johns Hopkins University, Baltimore, and his colleagues (Am J Emerg Med. 2019;37[2]:286-90).

“Given the substantial burden of HCV-related illness in urban ED patients nationally, and the recognized fact that EDs are often the only point of contact with the health care system for many of these patients, we propose incorporating FIB-4 based rapid assessment into ED-based HCV screening and LTC programs in order to prioritize LTC for patients with advanced liver fibrosis, as well as routine ED clinical practice,” the researchers concluded.

They reported having no conflicts.

[email protected]

SOURCE: Yu-Hsiang Hsieh Y-H, Am J Emerg Med. 2019;37[2]:286-90.

More than one-third of hepatitis C virus-infected patients in the emergency department (ED) were found to have advanced liver fibrosis and higher mortality, according to the results of a retrospective study of 113 known patients with HCV at a single institution.

Courtesy NIH

As part of an ongoing HCV linkage-to-care (LTC) program, HCV-infected ED patients were retrospectively identified. Components of FIB-4 (a noninvasive serum fibrosis index, which includes age, alanine aminotransferase, aspartate aminotransferase, and platelet count), were abstracted. Patients with an FIB-4 greater than 3.25 were classified with advanced fibrosis and characterized with regard to downstream outcomes at 1 year after enrollment.

The 1-year outcomes after the ED encounter for the 113 patients showed 38 with and 75 patients without advanced fibrosis. Among these, 72 (96%) and 34 (89.5%), respectively, agreed to be linked to HCV care. Ten patients of the total number of patients died within the 1-year follow-up. For those HCV-infected patients with advanced liver fibrosis compared to those without, all-cause mortality was more than fourfold higher, (18.4% [7 patients] vs. 4.0% [3 patients], P = .030), according to Yu-Hsiang Hsieh, PhD, associate professor of emergency medicine at Johns Hopkins University, Baltimore, and his colleagues (Am J Emerg Med. 2019;37[2]:286-90).

“Given the substantial burden of HCV-related illness in urban ED patients nationally, and the recognized fact that EDs are often the only point of contact with the health care system for many of these patients, we propose incorporating FIB-4 based rapid assessment into ED-based HCV screening and LTC programs in order to prioritize LTC for patients with advanced liver fibrosis, as well as routine ED clinical practice,” the researchers concluded.

They reported having no conflicts.

[email protected]

SOURCE: Yu-Hsiang Hsieh Y-H, Am J Emerg Med. 2019;37[2]:286-90.

WAIKOLOA, HAWAII – The best way to approach a patient with rosacea is to look at the individual symptoms, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Vidyard Video

Papules and pustules need an oral or topical anti-inflammatory drug. Background erythema requires an alpha adrenergic agonist. Telangiectasia is best handled by a laser device, and if a patient has a phyma, “you’ve got to use a surgical approach,” she said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. It sounds simple, but there are decisions to be made about what drugs and formulations to use, and when, and when to combine them.

In an interview, Dr. Stein Gold shared her approach to treatment, along with the latest on using ivermectin and brimonidine together, plus her thoughts on new medications under development and the role of the Demodex mite in rosacea.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The best way to approach a patient with rosacea is to look at the individual symptoms, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Vidyard Video

Papules and pustules need an oral or topical anti-inflammatory drug. Background erythema requires an alpha adrenergic agonist. Telangiectasia is best handled by a laser device, and if a patient has a phyma, “you’ve got to use a surgical approach,” she said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. It sounds simple, but there are decisions to be made about what drugs and formulations to use, and when, and when to combine them.

In an interview, Dr. Stein Gold shared her approach to treatment, along with the latest on using ivermectin and brimonidine together, plus her thoughts on new medications under development and the role of the Demodex mite in rosacea.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The best way to approach a patient with rosacea is to look at the individual symptoms, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Vidyard Video

Papules and pustules need an oral or topical anti-inflammatory drug. Background erythema requires an alpha adrenergic agonist. Telangiectasia is best handled by a laser device, and if a patient has a phyma, “you’ve got to use a surgical approach,” she said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. It sounds simple, but there are decisions to be made about what drugs and formulations to use, and when, and when to combine them.

In an interview, Dr. Stein Gold shared her approach to treatment, along with the latest on using ivermectin and brimonidine together, plus her thoughts on new medications under development and the role of the Demodex mite in rosacea.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

[email protected]

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

[email protected]

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

[email protected]

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

WASHINGTON – A bill requiring universal background checks for firearm purchases passed the House Judiciary committee and is expected to pass the full House of Representatives when it comes up for consideration.

Gregory Twachtman/MDedge

Rep. Mike Thompson (R-Calif.), chairman of the House Gun Violence Prevention Task Force, thanked the American Medical Association for its endorsement and support of the bill a day before its Feb. 13 committee passage during a speech at a national advocacy conference sponsored by the AMA.

“The new legislation, H.R. 8, which you have endorsed, would put in place universal background checks,” Rep. Thompson said. “This means anybody who buys a gun would have to go through a background check to make sure they are not a criminal, to make sure they are not dangerously mentally ill and a danger to themselves or others.”

The committee passed the Bipartisan Background Checks Act of 2019 by a 23-15 vote. It would require a background check on all firearms transfers, including private sales, with limited exemptions for firearms given as gifts between family members and those transferred for hunting, target shooting, and self-defense.

A second bill, the Enhanced Background Checks Act (H.R. 1112), passed 21-14 during the same session. That bill would close a loophole that currently allows a licensed dealer to transfer a firearm after 3 days if the background check system has not yet reported back.

Rep. Thompson credited the newest members of Congress with pushing these bills to the forefront.

“During the last midterm election, there was a sea change in attitude around gun violence prevention,” Rep. Thompson noted. “All 40 members of the Democratic-elected class who took a seat ran on gun violence prevention. So they came to Washington with more of a willingness to deal with this issue.”

H.R. 8 has 231 cosponsors – 226 Democrats and 5 Republicans – meaning it has more than enough support to pass in the full House, should all cosponsors remain on board.

Getting the bill passed in the Republican-controlled Senate will be a challenge and Rep. Thompson encouraged doctors to continue their advocacy on this legislation.

“You guys have been fabulous,” he said. “Without your help, we would not be where we are today. I can tell you that this bill will pass the House within the first 100 days and will go to the Senate. That is when you will have to start working again. ... Once it goes to the Senate, there is going to be a reluctance to take it up. We need to make sure that every U.S. senator hears from every doc and every doc’s family and every doc’s friend and every doc’s assistant and everybody else and their brother that this important so we can turn up the heat and make sure they take up the issue of background checks. It works. It saves lives.”
 

[email protected]

WASHINGTON – A bill requiring universal background checks for firearm purchases passed the House Judiciary committee and is expected to pass the full House of Representatives when it comes up for consideration.

Gregory Twachtman/MDedge

Rep. Mike Thompson (R-Calif.), chairman of the House Gun Violence Prevention Task Force, thanked the American Medical Association for its endorsement and support of the bill a day before its Feb. 13 committee passage during a speech at a national advocacy conference sponsored by the AMA.

“The new legislation, H.R. 8, which you have endorsed, would put in place universal background checks,” Rep. Thompson said. “This means anybody who buys a gun would have to go through a background check to make sure they are not a criminal, to make sure they are not dangerously mentally ill and a danger to themselves or others.”

The committee passed the Bipartisan Background Checks Act of 2019 by a 23-15 vote. It would require a background check on all firearms transfers, including private sales, with limited exemptions for firearms given as gifts between family members and those transferred for hunting, target shooting, and self-defense.

A second bill, the Enhanced Background Checks Act (H.R. 1112), passed 21-14 during the same session. That bill would close a loophole that currently allows a licensed dealer to transfer a firearm after 3 days if the background check system has not yet reported back.

Rep. Thompson credited the newest members of Congress with pushing these bills to the forefront.

“During the last midterm election, there was a sea change in attitude around gun violence prevention,” Rep. Thompson noted. “All 40 members of the Democratic-elected class who took a seat ran on gun violence prevention. So they came to Washington with more of a willingness to deal with this issue.”

H.R. 8 has 231 cosponsors – 226 Democrats and 5 Republicans – meaning it has more than enough support to pass in the full House, should all cosponsors remain on board.

Getting the bill passed in the Republican-controlled Senate will be a challenge and Rep. Thompson encouraged doctors to continue their advocacy on this legislation.

“You guys have been fabulous,” he said. “Without your help, we would not be where we are today. I can tell you that this bill will pass the House within the first 100 days and will go to the Senate. That is when you will have to start working again. ... Once it goes to the Senate, there is going to be a reluctance to take it up. We need to make sure that every U.S. senator hears from every doc and every doc’s family and every doc’s friend and every doc’s assistant and everybody else and their brother that this important so we can turn up the heat and make sure they take up the issue of background checks. It works. It saves lives.”
 

[email protected]

WASHINGTON – A bill requiring universal background checks for firearm purchases passed the House Judiciary committee and is expected to pass the full House of Representatives when it comes up for consideration.

Gregory Twachtman/MDedge

Rep. Mike Thompson (R-Calif.), chairman of the House Gun Violence Prevention Task Force, thanked the American Medical Association for its endorsement and support of the bill a day before its Feb. 13 committee passage during a speech at a national advocacy conference sponsored by the AMA.

“The new legislation, H.R. 8, which you have endorsed, would put in place universal background checks,” Rep. Thompson said. “This means anybody who buys a gun would have to go through a background check to make sure they are not a criminal, to make sure they are not dangerously mentally ill and a danger to themselves or others.”

The committee passed the Bipartisan Background Checks Act of 2019 by a 23-15 vote. It would require a background check on all firearms transfers, including private sales, with limited exemptions for firearms given as gifts between family members and those transferred for hunting, target shooting, and self-defense.

A second bill, the Enhanced Background Checks Act (H.R. 1112), passed 21-14 during the same session. That bill would close a loophole that currently allows a licensed dealer to transfer a firearm after 3 days if the background check system has not yet reported back.

Rep. Thompson credited the newest members of Congress with pushing these bills to the forefront.

“During the last midterm election, there was a sea change in attitude around gun violence prevention,” Rep. Thompson noted. “All 40 members of the Democratic-elected class who took a seat ran on gun violence prevention. So they came to Washington with more of a willingness to deal with this issue.”

H.R. 8 has 231 cosponsors – 226 Democrats and 5 Republicans – meaning it has more than enough support to pass in the full House, should all cosponsors remain on board.

Getting the bill passed in the Republican-controlled Senate will be a challenge and Rep. Thompson encouraged doctors to continue their advocacy on this legislation.

“You guys have been fabulous,” he said. “Without your help, we would not be where we are today. I can tell you that this bill will pass the House within the first 100 days and will go to the Senate. That is when you will have to start working again. ... Once it goes to the Senate, there is going to be a reluctance to take it up. We need to make sure that every U.S. senator hears from every doc and every doc’s family and every doc’s friend and every doc’s assistant and everybody else and their brother that this important so we can turn up the heat and make sure they take up the issue of background checks. It works. It saves lives.”
 

[email protected]

WAIKOLOA, HAWAII – There’s really not much reason to shy away from isotretinoin, spironolactone, and oral contraceptives for acne, according to Julie Harper, MD, of the department of dermatology at the University of Alabama at Birmingham.

There have been concerns with all three in the past, but most of the worries have been recently laid to rest.

The news hasn’t reached everyone, though, so, by and large, they are “tools I think we are not using enough of,” Dr. Harper said in an interview. With isotretinoin, for instance, it really isn’t necessary to do blood work for lipids and liver function every month, a daunting prospect for patients; baseline testing with a repeat at 2 months is sufficient, as long as there’s no dose escalation and results are acceptable, with the exception of a monthly pregnancy test for women, she noted. Meanwhile, there’s no evidence of a link with inflammatory bowel disease, and wound healing isn’t as much of an issue as once thought.

It’s the same story with spironolactone. Hyperkalemia is a long-standing concern, but it turns out that “in healthy young women taking spironolactone for acne, we don’t need to be checking potassium.” As far as breast cancer goes, the potential risk with spironolactone hasn’t panned out in the literature, and there may not be “a link at all,” Dr. Harper said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

There are caveats, of course. Hormonal treatments shouldn’t be used in young women until they’ve established their menstrual cycle. OCs should not be used in smokers, or people who have hypertension or migraines, among other conditions. Also, elevated triglycerides remain a concern with isotretinoin. “The number I would want people to remember is 500 [mg/dL],” the threshold when triglycerides become a problem.

In the interview, Dr. Harper explained the new thinking on these three options, and shared her treatment tips, including what to do if patients’ triglycerides hit the 500 mg/dL mark.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – There’s really not much reason to shy away from isotretinoin, spironolactone, and oral contraceptives for acne, according to Julie Harper, MD, of the department of dermatology at the University of Alabama at Birmingham.

There have been concerns with all three in the past, but most of the worries have been recently laid to rest.

The news hasn’t reached everyone, though, so, by and large, they are “tools I think we are not using enough of,” Dr. Harper said in an interview. With isotretinoin, for instance, it really isn’t necessary to do blood work for lipids and liver function every month, a daunting prospect for patients; baseline testing with a repeat at 2 months is sufficient, as long as there’s no dose escalation and results are acceptable, with the exception of a monthly pregnancy test for women, she noted. Meanwhile, there’s no evidence of a link with inflammatory bowel disease, and wound healing isn’t as much of an issue as once thought.

It’s the same story with spironolactone. Hyperkalemia is a long-standing concern, but it turns out that “in healthy young women taking spironolactone for acne, we don’t need to be checking potassium.” As far as breast cancer goes, the potential risk with spironolactone hasn’t panned out in the literature, and there may not be “a link at all,” Dr. Harper said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

There are caveats, of course. Hormonal treatments shouldn’t be used in young women until they’ve established their menstrual cycle. OCs should not be used in smokers, or people who have hypertension or migraines, among other conditions. Also, elevated triglycerides remain a concern with isotretinoin. “The number I would want people to remember is 500 [mg/dL],” the threshold when triglycerides become a problem.

In the interview, Dr. Harper explained the new thinking on these three options, and shared her treatment tips, including what to do if patients’ triglycerides hit the 500 mg/dL mark.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – There’s really not much reason to shy away from isotretinoin, spironolactone, and oral contraceptives for acne, according to Julie Harper, MD, of the department of dermatology at the University of Alabama at Birmingham.

There have been concerns with all three in the past, but most of the worries have been recently laid to rest.

The news hasn’t reached everyone, though, so, by and large, they are “tools I think we are not using enough of,” Dr. Harper said in an interview. With isotretinoin, for instance, it really isn’t necessary to do blood work for lipids and liver function every month, a daunting prospect for patients; baseline testing with a repeat at 2 months is sufficient, as long as there’s no dose escalation and results are acceptable, with the exception of a monthly pregnancy test for women, she noted. Meanwhile, there’s no evidence of a link with inflammatory bowel disease, and wound healing isn’t as much of an issue as once thought.

It’s the same story with spironolactone. Hyperkalemia is a long-standing concern, but it turns out that “in healthy young women taking spironolactone for acne, we don’t need to be checking potassium.” As far as breast cancer goes, the potential risk with spironolactone hasn’t panned out in the literature, and there may not be “a link at all,” Dr. Harper said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

There are caveats, of course. Hormonal treatments shouldn’t be used in young women until they’ve established their menstrual cycle. OCs should not be used in smokers, or people who have hypertension or migraines, among other conditions. Also, elevated triglycerides remain a concern with isotretinoin. “The number I would want people to remember is 500 [mg/dL],” the threshold when triglycerides become a problem.

In the interview, Dr. Harper explained the new thinking on these three options, and shared her treatment tips, including what to do if patients’ triglycerides hit the 500 mg/dL mark.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

With 26 new cases reported as of Feb. 14, 2019, the number of U.S. measles cases now stands at 127 for the year so far, according to the Centers for Disease Control and Prevention.

On Jan. 31, total measles cases stood at 79, which means that the number of individuals with measles has risen by 61% in just the last 2 weeks. Of the five outbreaks (defined as three or more cases) so far in 2019, three have occurred in New York (57 cases in three counties), one in Texas (8 cases in five counties), and one in Washington (62 cases in two counties), the CDC reported Feb. 18.

The majority of the Washington cases (61 of the 62) have occurred in Clark County, which is located just across the Columbia River from Portland, Ore. Oregon, in turn, has a higher percentage of kindergartners with nonmedical exemptions from vaccination (7.5%) than any other state, the CDC reported in October 2018. Washington’s rate of 3.9% was nearly double the national median of 2.0% for the 2017-2018 school year, while Texas (1.8%) and New York (1.0%) were below it, the CDC said.

In the Pacific Northwest, however, some parents may be changing their minds about vaccinations, according to the New York Times, which reported that “about triple the number of children have been vaccinated this year, compared with the same period in 2018,” in Oregon and southwest Washington.

Individual cases of measles have been reported to the CDC by seven other states: California, Colorado, Connecticut, Georgia, Illinois, Kentucky, and Oregon.

[email protected]

With 26 new cases reported as of Feb. 14, 2019, the number of U.S. measles cases now stands at 127 for the year so far, according to the Centers for Disease Control and Prevention.

On Jan. 31, total measles cases stood at 79, which means that the number of individuals with measles has risen by 61% in just the last 2 weeks. Of the five outbreaks (defined as three or more cases) so far in 2019, three have occurred in New York (57 cases in three counties), one in Texas (8 cases in five counties), and one in Washington (62 cases in two counties), the CDC reported Feb. 18.

The majority of the Washington cases (61 of the 62) have occurred in Clark County, which is located just across the Columbia River from Portland, Ore. Oregon, in turn, has a higher percentage of kindergartners with nonmedical exemptions from vaccination (7.5%) than any other state, the CDC reported in October 2018. Washington’s rate of 3.9% was nearly double the national median of 2.0% for the 2017-2018 school year, while Texas (1.8%) and New York (1.0%) were below it, the CDC said.

In the Pacific Northwest, however, some parents may be changing their minds about vaccinations, according to the New York Times, which reported that “about triple the number of children have been vaccinated this year, compared with the same period in 2018,” in Oregon and southwest Washington.

Individual cases of measles have been reported to the CDC by seven other states: California, Colorado, Connecticut, Georgia, Illinois, Kentucky, and Oregon.

[email protected]

With 26 new cases reported as of Feb. 14, 2019, the number of U.S. measles cases now stands at 127 for the year so far, according to the Centers for Disease Control and Prevention.

On Jan. 31, total measles cases stood at 79, which means that the number of individuals with measles has risen by 61% in just the last 2 weeks. Of the five outbreaks (defined as three or more cases) so far in 2019, three have occurred in New York (57 cases in three counties), one in Texas (8 cases in five counties), and one in Washington (62 cases in two counties), the CDC reported Feb. 18.

The majority of the Washington cases (61 of the 62) have occurred in Clark County, which is located just across the Columbia River from Portland, Ore. Oregon, in turn, has a higher percentage of kindergartners with nonmedical exemptions from vaccination (7.5%) than any other state, the CDC reported in October 2018. Washington’s rate of 3.9% was nearly double the national median of 2.0% for the 2017-2018 school year, while Texas (1.8%) and New York (1.0%) were below it, the CDC said.

In the Pacific Northwest, however, some parents may be changing their minds about vaccinations, according to the New York Times, which reported that “about triple the number of children have been vaccinated this year, compared with the same period in 2018,” in Oregon and southwest Washington.

Individual cases of measles have been reported to the CDC by seven other states: California, Colorado, Connecticut, Georgia, Illinois, Kentucky, and Oregon.

[email protected]

A total of 42 new drugs have been associated with drug-induced lupus in a study that mined the World Health Organization’s international pharmacovigilance drug monitoring database, leaving the overall number now standing at 118.

Artfoliophoto/Thinkstock

Among the 118 suspected drugs found in VigiBase, the WHO’s global deduplicated individual case safety reports (ICSR) database, 42 had not been previously reported in association with drug-induced lupus (DIL) and 76 had been previously reported in association with DIL in Medline. DIL was reported as a serious adverse event in 55.4% of cases, according to French researchers led by Laurent Arnaud, MD, PhD, of the department of rheumatology at Hôpitaux Universitaires de Strasbourg and Centre National de Références des Maladies Systémiques Rares, Strasbourg, France.

Dr. Arnaud and his colleagues conducted a case-noncase analysis for each drug associated with DIL in order to compare the proportion of specific adverse drug reactions (ADRs) reported for a single drug with the proportion of the same ADR for all other treatments in VigiBase, which receives reports from more than 130 country members of the WHO Programme for International Drug Monitoring and contains over 16 million deduplicated ICSRs recorded by pharmacovigilance centers since 1967. They searched for cases classified as systemic lupus erythematosus (SLE) and identified 12,166 ICSRs of DIL; from these they found 118 suspected drugs with significant pharmacovigilance signal from 8,163 ICSRs that mostly originated from the Americas (65%) and Europe (23%).

In line with what the study authors expected, the drugs associated with the highest number of DIL cases were the antitumor necrosis factor agents infliximab, adalimumab, and etanercept, and the drugs associated with the highest disproportional reporting of DIL were procainamide and hydralazine.

“This is an important finding because these are the two drugs associated with the highest risk of DIL in the literature, therefore confirming the reliability of our approach using a large pharmacovigilance database,” the researchers wrote in Annals of the Rheumatic Diseases.

Overall, DIL was considered definite for 9 drugs (procainamide, hydralazine, minocycline, quinidine, isoniazid, terbinafine, methyldopa, dihydralazine, and chlorpromazine), probable for 19 drugs, and possible for 45 drugs.

The median age of DIL onset was 49 years, which the authors noted was about 2 decades older than that of spontaneous SLE.

They also observed a marked predominance in females (female to male sex ratio, 4.3), a finding that contrasted with previous studies reporting a female to male sex ratio closer to 1:1.

Dr. Arnaud and his colleagues stated that their finding of a median delay between the reported start of suspected treatment and DIL occurrence of 172 days (interquartile range, 35-610 days) suggested that DIL mostly appears after a few months and usually within the first 2 years of treatment with the suspected drug.

“The analysis of the median reporting years for each suspected drug shows a clear evolution of suspected drugs during the past decades. This further underlines that the constantly changing spectrum of DIL should be monitored continuously, and further validates the interest of our approach using the WHO international pharmacovigilance database, the biggest database of this kind with over 16 million deduplicated ICSRs,” they wrote.

The researchers added that distinguishing DIL from SLE is important because its prognosis is usually good when the drug is withdrawn, but the spectrum of DIL is constantly evolving, with drugs once described as strongly linked to DIL now prescribed less frequently.

“The first case of DIL was reported in 1945 with sulfadiazine, while hydralazine DIL was first reported in 1953. Since then, pharmacopoeia has strongly evolved, and one could hypothesize that so has the spectrum of drugs that can induce DIL,” they wrote.

“The detailed list of suspected drugs may prove useful to physicians when confronted with potential DIL cases. Altogether, these findings may help in improving the identification of this constantly evolving disease,” they concluded.

The current study was limited by the lack of a uniform set of criteria for the diagnosis of DIL and by the level of reported details available in VigiBase.

The authors had no outside funding for the study and reported having no conflicts of interest.

SOURCE: Arnaud L et al. Ann Rheum Dis. 2019 Feb 4. doi: 10.1136/annrheumdis-2018-214598.

A total of 42 new drugs have been associated with drug-induced lupus in a study that mined the World Health Organization’s international pharmacovigilance drug monitoring database, leaving the overall number now standing at 118.

Artfoliophoto/Thinkstock

Among the 118 suspected drugs found in VigiBase, the WHO’s global deduplicated individual case safety reports (ICSR) database, 42 had not been previously reported in association with drug-induced lupus (DIL) and 76 had been previously reported in association with DIL in Medline. DIL was reported as a serious adverse event in 55.4% of cases, according to French researchers led by Laurent Arnaud, MD, PhD, of the department of rheumatology at Hôpitaux Universitaires de Strasbourg and Centre National de Références des Maladies Systémiques Rares, Strasbourg, France.

Dr. Arnaud and his colleagues conducted a case-noncase analysis for each drug associated with DIL in order to compare the proportion of specific adverse drug reactions (ADRs) reported for a single drug with the proportion of the same ADR for all other treatments in VigiBase, which receives reports from more than 130 country members of the WHO Programme for International Drug Monitoring and contains over 16 million deduplicated ICSRs recorded by pharmacovigilance centers since 1967. They searched for cases classified as systemic lupus erythematosus (SLE) and identified 12,166 ICSRs of DIL; from these they found 118 suspected drugs with significant pharmacovigilance signal from 8,163 ICSRs that mostly originated from the Americas (65%) and Europe (23%).

In line with what the study authors expected, the drugs associated with the highest number of DIL cases were the antitumor necrosis factor agents infliximab, adalimumab, and etanercept, and the drugs associated with the highest disproportional reporting of DIL were procainamide and hydralazine.

“This is an important finding because these are the two drugs associated with the highest risk of DIL in the literature, therefore confirming the reliability of our approach using a large pharmacovigilance database,” the researchers wrote in Annals of the Rheumatic Diseases.

Overall, DIL was considered definite for 9 drugs (procainamide, hydralazine, minocycline, quinidine, isoniazid, terbinafine, methyldopa, dihydralazine, and chlorpromazine), probable for 19 drugs, and possible for 45 drugs.

The median age of DIL onset was 49 years, which the authors noted was about 2 decades older than that of spontaneous SLE.

They also observed a marked predominance in females (female to male sex ratio, 4.3), a finding that contrasted with previous studies reporting a female to male sex ratio closer to 1:1.

Dr. Arnaud and his colleagues stated that their finding of a median delay between the reported start of suspected treatment and DIL occurrence of 172 days (interquartile range, 35-610 days) suggested that DIL mostly appears after a few months and usually within the first 2 years of treatment with the suspected drug.

“The analysis of the median reporting years for each suspected drug shows a clear evolution of suspected drugs during the past decades. This further underlines that the constantly changing spectrum of DIL should be monitored continuously, and further validates the interest of our approach using the WHO international pharmacovigilance database, the biggest database of this kind with over 16 million deduplicated ICSRs,” they wrote.

The researchers added that distinguishing DIL from SLE is important because its prognosis is usually good when the drug is withdrawn, but the spectrum of DIL is constantly evolving, with drugs once described as strongly linked to DIL now prescribed less frequently.

“The first case of DIL was reported in 1945 with sulfadiazine, while hydralazine DIL was first reported in 1953. Since then, pharmacopoeia has strongly evolved, and one could hypothesize that so has the spectrum of drugs that can induce DIL,” they wrote.

“The detailed list of suspected drugs may prove useful to physicians when confronted with potential DIL cases. Altogether, these findings may help in improving the identification of this constantly evolving disease,” they concluded.

The current study was limited by the lack of a uniform set of criteria for the diagnosis of DIL and by the level of reported details available in VigiBase.

The authors had no outside funding for the study and reported having no conflicts of interest.

SOURCE: Arnaud L et al. Ann Rheum Dis. 2019 Feb 4. doi: 10.1136/annrheumdis-2018-214598.

A total of 42 new drugs have been associated with drug-induced lupus in a study that mined the World Health Organization’s international pharmacovigilance drug monitoring database, leaving the overall number now standing at 118.

Artfoliophoto/Thinkstock

Among the 118 suspected drugs found in VigiBase, the WHO’s global deduplicated individual case safety reports (ICSR) database, 42 had not been previously reported in association with drug-induced lupus (DIL) and 76 had been previously reported in association with DIL in Medline. DIL was reported as a serious adverse event in 55.4% of cases, according to French researchers led by Laurent Arnaud, MD, PhD, of the department of rheumatology at Hôpitaux Universitaires de Strasbourg and Centre National de Références des Maladies Systémiques Rares, Strasbourg, France.

Dr. Arnaud and his colleagues conducted a case-noncase analysis for each drug associated with DIL in order to compare the proportion of specific adverse drug reactions (ADRs) reported for a single drug with the proportion of the same ADR for all other treatments in VigiBase, which receives reports from more than 130 country members of the WHO Programme for International Drug Monitoring and contains over 16 million deduplicated ICSRs recorded by pharmacovigilance centers since 1967. They searched for cases classified as systemic lupus erythematosus (SLE) and identified 12,166 ICSRs of DIL; from these they found 118 suspected drugs with significant pharmacovigilance signal from 8,163 ICSRs that mostly originated from the Americas (65%) and Europe (23%).

In line with what the study authors expected, the drugs associated with the highest number of DIL cases were the antitumor necrosis factor agents infliximab, adalimumab, and etanercept, and the drugs associated with the highest disproportional reporting of DIL were procainamide and hydralazine.

“This is an important finding because these are the two drugs associated with the highest risk of DIL in the literature, therefore confirming the reliability of our approach using a large pharmacovigilance database,” the researchers wrote in Annals of the Rheumatic Diseases.

Overall, DIL was considered definite for 9 drugs (procainamide, hydralazine, minocycline, quinidine, isoniazid, terbinafine, methyldopa, dihydralazine, and chlorpromazine), probable for 19 drugs, and possible for 45 drugs.

The median age of DIL onset was 49 years, which the authors noted was about 2 decades older than that of spontaneous SLE.

They also observed a marked predominance in females (female to male sex ratio, 4.3), a finding that contrasted with previous studies reporting a female to male sex ratio closer to 1:1.

Dr. Arnaud and his colleagues stated that their finding of a median delay between the reported start of suspected treatment and DIL occurrence of 172 days (interquartile range, 35-610 days) suggested that DIL mostly appears after a few months and usually within the first 2 years of treatment with the suspected drug.

“The analysis of the median reporting years for each suspected drug shows a clear evolution of suspected drugs during the past decades. This further underlines that the constantly changing spectrum of DIL should be monitored continuously, and further validates the interest of our approach using the WHO international pharmacovigilance database, the biggest database of this kind with over 16 million deduplicated ICSRs,” they wrote.

The researchers added that distinguishing DIL from SLE is important because its prognosis is usually good when the drug is withdrawn, but the spectrum of DIL is constantly evolving, with drugs once described as strongly linked to DIL now prescribed less frequently.

“The first case of DIL was reported in 1945 with sulfadiazine, while hydralazine DIL was first reported in 1953. Since then, pharmacopoeia has strongly evolved, and one could hypothesize that so has the spectrum of drugs that can induce DIL,” they wrote.

“The detailed list of suspected drugs may prove useful to physicians when confronted with potential DIL cases. Altogether, these findings may help in improving the identification of this constantly evolving disease,” they concluded.

The current study was limited by the lack of a uniform set of criteria for the diagnosis of DIL and by the level of reported details available in VigiBase.

The authors had no outside funding for the study and reported having no conflicts of interest.

SOURCE: Arnaud L et al. Ann Rheum Dis. 2019 Feb 4. doi: 10.1136/annrheumdis-2018-214598.