The combination of dasatinib and venetoclax had a synergistic effect that was associated with lower toxicity than single-agent therapy, based on responses of primary Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL) samples in xenografted immunodeficient mice, according to Jessica T. Leonard, MD.

Dr. Leonard and her colleagues at Oregon Health and Science University in Portland demonstrated that the combination of venetoclax – a selective inhibitor of B cell lymphoma 2 – was highly synergistic with tyrosine kinase inhibitors in vitro. In the preclinical model of PH+ALL, a stepwise reduction in median inhibitory concentration of dasatinib was observed with increasing doses of venetoclax, as was decreased cell viability and induced apoptosis. Dasatinib – a breakpoint cluster region–Abelson kinase inhibitor – has an additional advantage of potentially overcoming venetoclax resistance by blocking a common mechanism of resistance to the agent, the investigators reported Aug. 31 in Science Translational Medicine (2016; 8[354]:354ra114).

The combination boosted antitumor activity against Ph+ALL cells grown in culture. In the mouse model of Ph+ALL, all of the mice in the combination dosing group remained alive during the 4-week treatment period. The combination therapy was well tolerated, and superior to either agent alone with respect to antileukemic efficacy.

The investigators focused on combining venetoclax with dasatinib because it is “the current backbone for the treatment of adult Ph+ALL ... These results lay the foundation for the testing of this combination in patients with Ph+ALL with the goal of improving treatment,” they concluded.

This study was supported in part by the Leukemia & Lymphoma Society and the Newman’s Own Foundation. Dr. Leonard reported having no other disclosures, but various coauthors reported receiving research support from, and/or serving as a consultant or scientific advisory board member to Genentech, the maker of venetoclax, and Bristol-Myers Squibb, the maker of dasatinib, as well as numerous other drug companies.

[email protected]

The combination of dasatinib and venetoclax had a synergistic effect that was associated with lower toxicity than single-agent therapy, based on responses of primary Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL) samples in xenografted immunodeficient mice, according to Jessica T. Leonard, MD.

Dr. Leonard and her colleagues at Oregon Health and Science University in Portland demonstrated that the combination of venetoclax – a selective inhibitor of B cell lymphoma 2 – was highly synergistic with tyrosine kinase inhibitors in vitro. In the preclinical model of PH+ALL, a stepwise reduction in median inhibitory concentration of dasatinib was observed with increasing doses of venetoclax, as was decreased cell viability and induced apoptosis. Dasatinib – a breakpoint cluster region–Abelson kinase inhibitor – has an additional advantage of potentially overcoming venetoclax resistance by blocking a common mechanism of resistance to the agent, the investigators reported Aug. 31 in Science Translational Medicine (2016; 8[354]:354ra114).

The combination boosted antitumor activity against Ph+ALL cells grown in culture. In the mouse model of Ph+ALL, all of the mice in the combination dosing group remained alive during the 4-week treatment period. The combination therapy was well tolerated, and superior to either agent alone with respect to antileukemic efficacy.

The investigators focused on combining venetoclax with dasatinib because it is “the current backbone for the treatment of adult Ph+ALL ... These results lay the foundation for the testing of this combination in patients with Ph+ALL with the goal of improving treatment,” they concluded.

This study was supported in part by the Leukemia & Lymphoma Society and the Newman’s Own Foundation. Dr. Leonard reported having no other disclosures, but various coauthors reported receiving research support from, and/or serving as a consultant or scientific advisory board member to Genentech, the maker of venetoclax, and Bristol-Myers Squibb, the maker of dasatinib, as well as numerous other drug companies.

[email protected]

The combination of dasatinib and venetoclax had a synergistic effect that was associated with lower toxicity than single-agent therapy, based on responses of primary Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL) samples in xenografted immunodeficient mice, according to Jessica T. Leonard, MD.

Dr. Leonard and her colleagues at Oregon Health and Science University in Portland demonstrated that the combination of venetoclax – a selective inhibitor of B cell lymphoma 2 – was highly synergistic with tyrosine kinase inhibitors in vitro. In the preclinical model of PH+ALL, a stepwise reduction in median inhibitory concentration of dasatinib was observed with increasing doses of venetoclax, as was decreased cell viability and induced apoptosis. Dasatinib – a breakpoint cluster region–Abelson kinase inhibitor – has an additional advantage of potentially overcoming venetoclax resistance by blocking a common mechanism of resistance to the agent, the investigators reported Aug. 31 in Science Translational Medicine (2016; 8[354]:354ra114).

The combination boosted antitumor activity against Ph+ALL cells grown in culture. In the mouse model of Ph+ALL, all of the mice in the combination dosing group remained alive during the 4-week treatment period. The combination therapy was well tolerated, and superior to either agent alone with respect to antileukemic efficacy.

The investigators focused on combining venetoclax with dasatinib because it is “the current backbone for the treatment of adult Ph+ALL ... These results lay the foundation for the testing of this combination in patients with Ph+ALL with the goal of improving treatment,” they concluded.

This study was supported in part by the Leukemia & Lymphoma Society and the Newman’s Own Foundation. Dr. Leonard reported having no other disclosures, but various coauthors reported receiving research support from, and/or serving as a consultant or scientific advisory board member to Genentech, the maker of venetoclax, and Bristol-Myers Squibb, the maker of dasatinib, as well as numerous other drug companies.

[email protected]

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

[email protected]

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

[email protected]

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

A genetic modification of the plasminogen activator inhibitor-1 gene in conjunction with lower respiratory infections during early life was associated with increased risk of asthma, morbidities, and reduced lung function, according to Seong H. Cho, MD, and his associates.

A history of respiratory syncytial virus (RSV) and a history of other lower respiratory infections (LRIs) before the age of 2 were independently associated with asthma in Latino people aged 8-21, with odd ratios of 9.9 and 9.1, respectively, while PAI-1 was not independently associated. In combination, the OR for PAI-1/RSV increased to 17.7, and the OR for PAI-1/other LRIs increased to 11.7.

©SilverV/Thinkstock

Lung function was also adversely affected by the joint effect of PAI-1 and early life infection. In patients with PAI-1/LRI, forced expiratory volume in 1 second (FEV₁₎ percent predicted and FEV₁/forced vital capacity (FVC) percent predicted were significantly less than in the control group. Similar but less significant results were seen in the PAI-1/RSV group. Recurring hospitalizations were also significantly more likely in the PAI-1/RSV group, with an OR of 3.1.

“Further prospective studies are needed to replicate our RSV-genotype findings in other non-Latino populations, and determine if PAI-1 variants may serve as a biomarker of risk, which may provide impetus for clinical trials of primary prevention of asthma. In the interim, PAI-1 genotype in combination with significant LRI identifies individuals at increased risk of developing asthma,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0157848).

[email protected]

A genetic modification of the plasminogen activator inhibitor-1 gene in conjunction with lower respiratory infections during early life was associated with increased risk of asthma, morbidities, and reduced lung function, according to Seong H. Cho, MD, and his associates.

A history of respiratory syncytial virus (RSV) and a history of other lower respiratory infections (LRIs) before the age of 2 were independently associated with asthma in Latino people aged 8-21, with odd ratios of 9.9 and 9.1, respectively, while PAI-1 was not independently associated. In combination, the OR for PAI-1/RSV increased to 17.7, and the OR for PAI-1/other LRIs increased to 11.7.

©SilverV/Thinkstock

Lung function was also adversely affected by the joint effect of PAI-1 and early life infection. In patients with PAI-1/LRI, forced expiratory volume in 1 second (FEV₁₎ percent predicted and FEV₁/forced vital capacity (FVC) percent predicted were significantly less than in the control group. Similar but less significant results were seen in the PAI-1/RSV group. Recurring hospitalizations were also significantly more likely in the PAI-1/RSV group, with an OR of 3.1.

“Further prospective studies are needed to replicate our RSV-genotype findings in other non-Latino populations, and determine if PAI-1 variants may serve as a biomarker of risk, which may provide impetus for clinical trials of primary prevention of asthma. In the interim, PAI-1 genotype in combination with significant LRI identifies individuals at increased risk of developing asthma,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0157848).

[email protected]

A genetic modification of the plasminogen activator inhibitor-1 gene in conjunction with lower respiratory infections during early life was associated with increased risk of asthma, morbidities, and reduced lung function, according to Seong H. Cho, MD, and his associates.

A history of respiratory syncytial virus (RSV) and a history of other lower respiratory infections (LRIs) before the age of 2 were independently associated with asthma in Latino people aged 8-21, with odd ratios of 9.9 and 9.1, respectively, while PAI-1 was not independently associated. In combination, the OR for PAI-1/RSV increased to 17.7, and the OR for PAI-1/other LRIs increased to 11.7.

©SilverV/Thinkstock

Lung function was also adversely affected by the joint effect of PAI-1 and early life infection. In patients with PAI-1/LRI, forced expiratory volume in 1 second (FEV₁₎ percent predicted and FEV₁/forced vital capacity (FVC) percent predicted were significantly less than in the control group. Similar but less significant results were seen in the PAI-1/RSV group. Recurring hospitalizations were also significantly more likely in the PAI-1/RSV group, with an OR of 3.1.

“Further prospective studies are needed to replicate our RSV-genotype findings in other non-Latino populations, and determine if PAI-1 variants may serve as a biomarker of risk, which may provide impetus for clinical trials of primary prevention of asthma. In the interim, PAI-1 genotype in combination with significant LRI identifies individuals at increased risk of developing asthma,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0157848).

[email protected]

Case Report

A 24-year-old man was referred to the dermatology department for evaluation of pustules, atrophic scars, and alopecia on the scalp of 6 years’ duration. Six years prior, erythema, scaling, and follicular keratotic papules had appeared on the superciliary arches, and he started to lose hair from the eyebrows. Three months later, he developed mildly pruritic and painful scaling and pustules on the scalp. These lesions resolved with atrophic scarring accompanied by alopecia. One year later, follicular keratotic papules developed on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae. Two years later, direct microscopy of the lesions on the scalp and fungal culture were negative. After 2 weeks of treatment with roxithromycin (0.15 g twice daily), the scalp pustules dried out and resolved; however, they recurred when the patient stopped taking the medication. Six months later, he was started on isotretinoin treatment (10 mg once daily) for half a year, but no improvement was seen. His parents were nonconsanguineous, and no other family members were affected.

Dermatologic examination revealed large areas of atrophic scarring and alopecia on the scalp. Only a few solitary hairs remained on the top of the head, with the follicles surrounded by keratotic papules, pustules, and black scabs. There was sparse hair on the forehead and temples and scattered hair clusters in the occipital region near the hairline. These follicles also were associated with keratotic papules (Figure 1A). Erythema, scales, and follicular keratotic papules of the superciliary arches with sparse eyebrows and axillary hairs were noted. Follicular keratotic papules also were observed on the cheeks, axillae, chest, abdomen, back, lateral upper arms, and thighs. Dental examination revealed a large space between the upper anterior teeth and the lower anterior teeth. The upper anterior teeth were anteverted, there was congenital absence of right lower central incisors, and the anterior teeth were in deep overbite and overjet (Figure 1B). There was gingival atrophy and calculus dentalis in the upper and lower teeth. He had a fissured tongue with atrophic filiform papillae (Figure 1C).

Comment

Folliculitis spinulosa decalvans, along with keratosis follicularis spinulosa decalvans (KFSD), keratosis pilaris atrophicans faciei, and atrophoderma vermiculatum, belongs to a group of diseases that includes keratosis pilaris atrophicans. In 1994, Oranje et al¹ suggested the term folliculitis spinulosa decalvans, with signs including persistent pustules, characteristic keratotic papules, and scarring alopecia of the scalp, which may be exacerbated at puberty. Staphylococcus aureus was isolated from the pustules in one study²; however, in another study, repeated cultures were negative.³ Although the main inheritance pattern of KFSD is X-linked, autosomal-dominant inheritance is more common in FSD. Furthermore, there are certain differences in the clinical manifestations of these 2 conditions. Therefore, it remains controversial if FSD is an independent disease or merely a subtype of KFSD.

Our patient’s symptoms manifested after puberty, primarily pustules as well as atrophic and scarring alopecia of the scalp and follicular keratotic papules on the head, face, trunk, lateral upper arms, and thighs. Pathologic examination showed massive infiltration of plasma cells, neutrophils, and multinucleated giant cells around the hair follicles. The clinical and histopathologic findings met the diagnostic criteria for FSD.

Folliculitis spinulosa decalvans is a rare clinical condition with few cases reported.^3-5 In addition to the aforementioned characteristic clinical manifestations, our patient also had dental anomalies, a fissured tongue, and atrophy of the tongue papillae, which are not known to be associated with FSD. Dental anomalies are characteristic of patients with Down syndrome, ectodermal dysplasia, Papillon-Lefèvre syndrome, and other conditions.⁶ Fissured tongue is a normal variant that occurs in 5% to 11% of individuals. It also is a classic but nonspecific feature of Melkersson-Rosenthal syndrome and may occur in psoriasis, Down syndrome, acromegaly, and Sjögren syndrome.⁷ Atrophy of the tongue papillae is associated with anemia, pellagra, Sjögren syndrome, candidiasis, and other conditions.⁸ Because there are no known reports of associations between FSD and any of these oral manifestations, it is possible that they were unrelated to FSD in our patient.

Folliculitis spinulosa decalvans usually is recurrent and there is no consistently effective treatment for it. Kunte et al⁴ reported that dapsone (100 mg/d) led to resolution of scalp inflammation and pustules within 1 month. Romine et al² reported that a 3-week course of dichloroxacillin (250 mg 4 times daily) induced disappearance of pustules around the hair follicles. However, Hallai et al⁵ reported a patient who was resistant to isotretinoin treatment. In our case, after 1 month of treatment with clarithromycin, metronidazole, viaminate, and fusidic acid cream, the pustules had resolved and the black scabs had fallen off, leaving atrophic scars. The long-term efficacy of this regimen is still under observation.

Conclusion

We report a case of FSD with dental anomalies, a fissured tongue, and atrophy of tongue papillae, none of which have previously been reported in association with FSD. We, therefore, believe that our patient’s oral manifestations are unrelated to FSD.

Case Report

A 24-year-old man was referred to the dermatology department for evaluation of pustules, atrophic scars, and alopecia on the scalp of 6 years’ duration. Six years prior, erythema, scaling, and follicular keratotic papules had appeared on the superciliary arches, and he started to lose hair from the eyebrows. Three months later, he developed mildly pruritic and painful scaling and pustules on the scalp. These lesions resolved with atrophic scarring accompanied by alopecia. One year later, follicular keratotic papules developed on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae. Two years later, direct microscopy of the lesions on the scalp and fungal culture were negative. After 2 weeks of treatment with roxithromycin (0.15 g twice daily), the scalp pustules dried out and resolved; however, they recurred when the patient stopped taking the medication. Six months later, he was started on isotretinoin treatment (10 mg once daily) for half a year, but no improvement was seen. His parents were nonconsanguineous, and no other family members were affected.

Dermatologic examination revealed large areas of atrophic scarring and alopecia on the scalp. Only a few solitary hairs remained on the top of the head, with the follicles surrounded by keratotic papules, pustules, and black scabs. There was sparse hair on the forehead and temples and scattered hair clusters in the occipital region near the hairline. These follicles also were associated with keratotic papules (Figure 1A). Erythema, scales, and follicular keratotic papules of the superciliary arches with sparse eyebrows and axillary hairs were noted. Follicular keratotic papules also were observed on the cheeks, axillae, chest, abdomen, back, lateral upper arms, and thighs. Dental examination revealed a large space between the upper anterior teeth and the lower anterior teeth. The upper anterior teeth were anteverted, there was congenital absence of right lower central incisors, and the anterior teeth were in deep overbite and overjet (Figure 1B). There was gingival atrophy and calculus dentalis in the upper and lower teeth. He had a fissured tongue with atrophic filiform papillae (Figure 1C).

Comment

Folliculitis spinulosa decalvans, along with keratosis follicularis spinulosa decalvans (KFSD), keratosis pilaris atrophicans faciei, and atrophoderma vermiculatum, belongs to a group of diseases that includes keratosis pilaris atrophicans. In 1994, Oranje et al¹ suggested the term folliculitis spinulosa decalvans, with signs including persistent pustules, characteristic keratotic papules, and scarring alopecia of the scalp, which may be exacerbated at puberty. Staphylococcus aureus was isolated from the pustules in one study²; however, in another study, repeated cultures were negative.³ Although the main inheritance pattern of KFSD is X-linked, autosomal-dominant inheritance is more common in FSD. Furthermore, there are certain differences in the clinical manifestations of these 2 conditions. Therefore, it remains controversial if FSD is an independent disease or merely a subtype of KFSD.

Our patient’s symptoms manifested after puberty, primarily pustules as well as atrophic and scarring alopecia of the scalp and follicular keratotic papules on the head, face, trunk, lateral upper arms, and thighs. Pathologic examination showed massive infiltration of plasma cells, neutrophils, and multinucleated giant cells around the hair follicles. The clinical and histopathologic findings met the diagnostic criteria for FSD.

Folliculitis spinulosa decalvans is a rare clinical condition with few cases reported.^3-5 In addition to the aforementioned characteristic clinical manifestations, our patient also had dental anomalies, a fissured tongue, and atrophy of the tongue papillae, which are not known to be associated with FSD. Dental anomalies are characteristic of patients with Down syndrome, ectodermal dysplasia, Papillon-Lefèvre syndrome, and other conditions.⁶ Fissured tongue is a normal variant that occurs in 5% to 11% of individuals. It also is a classic but nonspecific feature of Melkersson-Rosenthal syndrome and may occur in psoriasis, Down syndrome, acromegaly, and Sjögren syndrome.⁷ Atrophy of the tongue papillae is associated with anemia, pellagra, Sjögren syndrome, candidiasis, and other conditions.⁸ Because there are no known reports of associations between FSD and any of these oral manifestations, it is possible that they were unrelated to FSD in our patient.

Folliculitis spinulosa decalvans usually is recurrent and there is no consistently effective treatment for it. Kunte et al⁴ reported that dapsone (100 mg/d) led to resolution of scalp inflammation and pustules within 1 month. Romine et al² reported that a 3-week course of dichloroxacillin (250 mg 4 times daily) induced disappearance of pustules around the hair follicles. However, Hallai et al⁵ reported a patient who was resistant to isotretinoin treatment. In our case, after 1 month of treatment with clarithromycin, metronidazole, viaminate, and fusidic acid cream, the pustules had resolved and the black scabs had fallen off, leaving atrophic scars. The long-term efficacy of this regimen is still under observation.

Conclusion

We report a case of FSD with dental anomalies, a fissured tongue, and atrophy of tongue papillae, none of which have previously been reported in association with FSD. We, therefore, believe that our patient’s oral manifestations are unrelated to FSD.

Case Report

A 24-year-old man was referred to the dermatology department for evaluation of pustules, atrophic scars, and alopecia on the scalp of 6 years’ duration. Six years prior, erythema, scaling, and follicular keratotic papules had appeared on the superciliary arches, and he started to lose hair from the eyebrows. Three months later, he developed mildly pruritic and painful scaling and pustules on the scalp. These lesions resolved with atrophic scarring accompanied by alopecia. One year later, follicular keratotic papules developed on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae. Two years later, direct microscopy of the lesions on the scalp and fungal culture were negative. After 2 weeks of treatment with roxithromycin (0.15 g twice daily), the scalp pustules dried out and resolved; however, they recurred when the patient stopped taking the medication. Six months later, he was started on isotretinoin treatment (10 mg once daily) for half a year, but no improvement was seen. His parents were nonconsanguineous, and no other family members were affected.

Dermatologic examination revealed large areas of atrophic scarring and alopecia on the scalp. Only a few solitary hairs remained on the top of the head, with the follicles surrounded by keratotic papules, pustules, and black scabs. There was sparse hair on the forehead and temples and scattered hair clusters in the occipital region near the hairline. These follicles also were associated with keratotic papules (Figure 1A). Erythema, scales, and follicular keratotic papules of the superciliary arches with sparse eyebrows and axillary hairs were noted. Follicular keratotic papules also were observed on the cheeks, axillae, chest, abdomen, back, lateral upper arms, and thighs. Dental examination revealed a large space between the upper anterior teeth and the lower anterior teeth. The upper anterior teeth were anteverted, there was congenital absence of right lower central incisors, and the anterior teeth were in deep overbite and overjet (Figure 1B). There was gingival atrophy and calculus dentalis in the upper and lower teeth. He had a fissured tongue with atrophic filiform papillae (Figure 1C).

Comment

Folliculitis spinulosa decalvans, along with keratosis follicularis spinulosa decalvans (KFSD), keratosis pilaris atrophicans faciei, and atrophoderma vermiculatum, belongs to a group of diseases that includes keratosis pilaris atrophicans. In 1994, Oranje et al¹ suggested the term folliculitis spinulosa decalvans, with signs including persistent pustules, characteristic keratotic papules, and scarring alopecia of the scalp, which may be exacerbated at puberty. Staphylococcus aureus was isolated from the pustules in one study²; however, in another study, repeated cultures were negative.³ Although the main inheritance pattern of KFSD is X-linked, autosomal-dominant inheritance is more common in FSD. Furthermore, there are certain differences in the clinical manifestations of these 2 conditions. Therefore, it remains controversial if FSD is an independent disease or merely a subtype of KFSD.

Our patient’s symptoms manifested after puberty, primarily pustules as well as atrophic and scarring alopecia of the scalp and follicular keratotic papules on the head, face, trunk, lateral upper arms, and thighs. Pathologic examination showed massive infiltration of plasma cells, neutrophils, and multinucleated giant cells around the hair follicles. The clinical and histopathologic findings met the diagnostic criteria for FSD.

Folliculitis spinulosa decalvans is a rare clinical condition with few cases reported.^3-5 In addition to the aforementioned characteristic clinical manifestations, our patient also had dental anomalies, a fissured tongue, and atrophy of the tongue papillae, which are not known to be associated with FSD. Dental anomalies are characteristic of patients with Down syndrome, ectodermal dysplasia, Papillon-Lefèvre syndrome, and other conditions.⁶ Fissured tongue is a normal variant that occurs in 5% to 11% of individuals. It also is a classic but nonspecific feature of Melkersson-Rosenthal syndrome and may occur in psoriasis, Down syndrome, acromegaly, and Sjögren syndrome.⁷ Atrophy of the tongue papillae is associated with anemia, pellagra, Sjögren syndrome, candidiasis, and other conditions.⁸ Because there are no known reports of associations between FSD and any of these oral manifestations, it is possible that they were unrelated to FSD in our patient.

Folliculitis spinulosa decalvans usually is recurrent and there is no consistently effective treatment for it. Kunte et al⁴ reported that dapsone (100 mg/d) led to resolution of scalp inflammation and pustules within 1 month. Romine et al² reported that a 3-week course of dichloroxacillin (250 mg 4 times daily) induced disappearance of pustules around the hair follicles. However, Hallai et al⁵ reported a patient who was resistant to isotretinoin treatment. In our case, after 1 month of treatment with clarithromycin, metronidazole, viaminate, and fusidic acid cream, the pustules had resolved and the black scabs had fallen off, leaving atrophic scars. The long-term efficacy of this regimen is still under observation.

Conclusion

We report a case of FSD with dental anomalies, a fissured tongue, and atrophy of tongue papillae, none of which have previously been reported in association with FSD. We, therefore, believe that our patient’s oral manifestations are unrelated to FSD.

The term nevus spilus (NS), also known as speckled lentiginous nevus, was first used in the 19th century to describe lesions with background café au lait–like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. The dark spots reflect lentigines; junctional, compound, and intradermal nevus cell nests; and more rarely Spitz and blue nevi. Both macular and papular subtypes have been described.¹ This birthmark is quite common, occurring in 1.3% to 2.3% of the adult population worldwide.² Hypertrichosis has been described in NS.^3-9 Two subsequent cases of malignant melanoma in hairy NS suggested that lesions may be particularly prone to malignant degeneration.^4,8 We report an additional case of hairy NS that was not associated with melanoma and consider whether dermatologists should warn their patients about this association.

Case Report

A 26-year-old woman presented with a stable 7×8-cm, tan-brown, macular, pigmented birthmark studded with darker 1- to 2-mm, irregular, brown-black and blue, confettilike macules on the left proximal lateral thigh that had been present since birth (Figure 1). Dark terminal hairs were present, arising from both the darker and lighter pigmented areas but not the surrounding normal skin.

A 4-mm punch biopsy from one of the dark blue macules demonstrated uniform lentiginous melanocytic hyperplasia and nevus cell nests adjacent to the sweat glands extending into the mid dermis (Figure 2). No clinical evidence of malignant degeneration was present.

Comment

The risk for melanoma is increased in classic nonspeckled congenital nevi and the risk correlates with the size of the lesion and most probably the number of nevus cells in the lesion that increase the risk for a random mutation.^8,10,11 It is likely that NS with or without hair presages a small increased risk for melanoma,^6,9,12 which is not surprising because NS is a subtype of congenital melanocytic nevus (CMN), a condition that is present at birth and results from a proliferation of melanocytes.⁶ Nevus spilus, however, appears to have a notably lower risk for malignant degeneration than other classic CMN of the same size. The following support for this hypothesis is offered: First, CMN have nevus cells broadly filling the dermis that extend more deeply into the dermis than NS (Figure 2A).¹⁰ In our estimation, CMN have at least 100 times the number of nevus cells per square centimeter compared to NS. The potential for malignant degeneration of any one melanocyte is greater when more are present. Second, although some NS lesions evolve, classic CMN are universally more proliferative than NS.^10,13 The involved skin in CMN thickens over time with increased numbers of melanocytes and marked overgrowth of adjacent tissue. Melanocytes in a proliferative phase may be more likely to undergo malignant degeneration.¹⁰

A PubMed search of articles indexed for MEDLINE using the search term nevus spilus and melanoma yielded 2 cases^4,8 of melanoma arising among 15 cases of hairy NS in the literature, which led to the suggestion that the presence of hair could be associated with an increased risk for malignant degeneration in NS (Table). This apparent high incidence of melanoma most likely reflects referral/publication bias rather than a statistically significant association. In fact, the clinical lesion most clinically similar to hairy NS is Becker nevus, with tan macules demonstrating lentiginous melanocytic hyperplasia associated with numerous coarse terminal hairs. There is no indication that Becker nevi have a considerable premalignant potential, though one case of melanoma arising in a Becker nevus has been reported.⁹ There is no evidence to suggest that classic CMN with hypertrichosis has a greater premalignant potential than similar lesions without hypertrichosis.

The term nevus spilus (NS), also known as speckled lentiginous nevus, was first used in the 19th century to describe lesions with background café au lait–like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. The dark spots reflect lentigines; junctional, compound, and intradermal nevus cell nests; and more rarely Spitz and blue nevi. Both macular and papular subtypes have been described.¹ This birthmark is quite common, occurring in 1.3% to 2.3% of the adult population worldwide.² Hypertrichosis has been described in NS.^3-9 Two subsequent cases of malignant melanoma in hairy NS suggested that lesions may be particularly prone to malignant degeneration.^4,8 We report an additional case of hairy NS that was not associated with melanoma and consider whether dermatologists should warn their patients about this association.

Case Report

A 26-year-old woman presented with a stable 7×8-cm, tan-brown, macular, pigmented birthmark studded with darker 1- to 2-mm, irregular, brown-black and blue, confettilike macules on the left proximal lateral thigh that had been present since birth (Figure 1). Dark terminal hairs were present, arising from both the darker and lighter pigmented areas but not the surrounding normal skin.

A 4-mm punch biopsy from one of the dark blue macules demonstrated uniform lentiginous melanocytic hyperplasia and nevus cell nests adjacent to the sweat glands extending into the mid dermis (Figure 2). No clinical evidence of malignant degeneration was present.

Comment

The risk for melanoma is increased in classic nonspeckled congenital nevi and the risk correlates with the size of the lesion and most probably the number of nevus cells in the lesion that increase the risk for a random mutation.^8,10,11 It is likely that NS with or without hair presages a small increased risk for melanoma,^6,9,12 which is not surprising because NS is a subtype of congenital melanocytic nevus (CMN), a condition that is present at birth and results from a proliferation of melanocytes.⁶ Nevus spilus, however, appears to have a notably lower risk for malignant degeneration than other classic CMN of the same size. The following support for this hypothesis is offered: First, CMN have nevus cells broadly filling the dermis that extend more deeply into the dermis than NS (Figure 2A).¹⁰ In our estimation, CMN have at least 100 times the number of nevus cells per square centimeter compared to NS. The potential for malignant degeneration of any one melanocyte is greater when more are present. Second, although some NS lesions evolve, classic CMN are universally more proliferative than NS.^10,13 The involved skin in CMN thickens over time with increased numbers of melanocytes and marked overgrowth of adjacent tissue. Melanocytes in a proliferative phase may be more likely to undergo malignant degeneration.¹⁰

A PubMed search of articles indexed for MEDLINE using the search term nevus spilus and melanoma yielded 2 cases^4,8 of melanoma arising among 15 cases of hairy NS in the literature, which led to the suggestion that the presence of hair could be associated with an increased risk for malignant degeneration in NS (Table). This apparent high incidence of melanoma most likely reflects referral/publication bias rather than a statistically significant association. In fact, the clinical lesion most clinically similar to hairy NS is Becker nevus, with tan macules demonstrating lentiginous melanocytic hyperplasia associated with numerous coarse terminal hairs. There is no indication that Becker nevi have a considerable premalignant potential, though one case of melanoma arising in a Becker nevus has been reported.⁹ There is no evidence to suggest that classic CMN with hypertrichosis has a greater premalignant potential than similar lesions without hypertrichosis.

The term nevus spilus (NS), also known as speckled lentiginous nevus, was first used in the 19th century to describe lesions with background café au lait–like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. The dark spots reflect lentigines; junctional, compound, and intradermal nevus cell nests; and more rarely Spitz and blue nevi. Both macular and papular subtypes have been described.¹ This birthmark is quite common, occurring in 1.3% to 2.3% of the adult population worldwide.² Hypertrichosis has been described in NS.^3-9 Two subsequent cases of malignant melanoma in hairy NS suggested that lesions may be particularly prone to malignant degeneration.^4,8 We report an additional case of hairy NS that was not associated with melanoma and consider whether dermatologists should warn their patients about this association.

Case Report

A 26-year-old woman presented with a stable 7×8-cm, tan-brown, macular, pigmented birthmark studded with darker 1- to 2-mm, irregular, brown-black and blue, confettilike macules on the left proximal lateral thigh that had been present since birth (Figure 1). Dark terminal hairs were present, arising from both the darker and lighter pigmented areas but not the surrounding normal skin.

A 4-mm punch biopsy from one of the dark blue macules demonstrated uniform lentiginous melanocytic hyperplasia and nevus cell nests adjacent to the sweat glands extending into the mid dermis (Figure 2). No clinical evidence of malignant degeneration was present.

Comment

The risk for melanoma is increased in classic nonspeckled congenital nevi and the risk correlates with the size of the lesion and most probably the number of nevus cells in the lesion that increase the risk for a random mutation.^8,10,11 It is likely that NS with or without hair presages a small increased risk for melanoma,^6,9,12 which is not surprising because NS is a subtype of congenital melanocytic nevus (CMN), a condition that is present at birth and results from a proliferation of melanocytes.⁶ Nevus spilus, however, appears to have a notably lower risk for malignant degeneration than other classic CMN of the same size. The following support for this hypothesis is offered: First, CMN have nevus cells broadly filling the dermis that extend more deeply into the dermis than NS (Figure 2A).¹⁰ In our estimation, CMN have at least 100 times the number of nevus cells per square centimeter compared to NS. The potential for malignant degeneration of any one melanocyte is greater when more are present. Second, although some NS lesions evolve, classic CMN are universally more proliferative than NS.^10,13 The involved skin in CMN thickens over time with increased numbers of melanocytes and marked overgrowth of adjacent tissue. Melanocytes in a proliferative phase may be more likely to undergo malignant degeneration.¹⁰

A PubMed search of articles indexed for MEDLINE using the search term nevus spilus and melanoma yielded 2 cases^4,8 of melanoma arising among 15 cases of hairy NS in the literature, which led to the suggestion that the presence of hair could be associated with an increased risk for malignant degeneration in NS (Table). This apparent high incidence of melanoma most likely reflects referral/publication bias rather than a statistically significant association. In fact, the clinical lesion most clinically similar to hairy NS is Becker nevus, with tan macules demonstrating lentiginous melanocytic hyperplasia associated with numerous coarse terminal hairs. There is no indication that Becker nevi have a considerable premalignant potential, though one case of melanoma arising in a Becker nevus has been reported.⁹ There is no evidence to suggest that classic CMN with hypertrichosis has a greater premalignant potential than similar lesions without hypertrichosis.

Atopic dermatitis (AD) is the most common inflammatory skin disease in both adults and children.¹ Unfortunately, the current treatment armamentarium is largely confined to topical calcineurin inhibitors, topical and systemic steroids, phototherapy, cyclosporine (not approved by the US Food and Drug Administration for AD), and other oral immunosuppressants.² The availability of partially helpful and highly toxic treatments creates a huge unmet need for more effective and safer treatments, particularly for patients with moderate to severe AD who often require systemic approaches.

Recent extensive translational (bench top to bedside and back) investigations in skin of AD patients has shown that skin phenotype is characterized by increased T-cell infiltration and related inflammatory cytokines as well as epidermal abnormalities (eg, hyperplasia, aberrant differentiation).³ Clinical improvement of AD has been demonstrated with broad T-cell targeted therapeutics, such as cyclosporine and narrowband UVB, coupled with decreases of T-cell infiltrates and inflammatory gene products as well as improvement of the pathologic epidermal phenotype.^4,5

In the past, AD was conceptualized as a T helper cell T_H2 (acute disease)/T_H1 (chronic disease) bipolar cytokine disorder.⁶ Acute lesions are characterized by high T_H2, T_H22, and some T_H17 signals, with intensification of these axes and T_H1 augmentation orchestrating the chronic phenotype.⁷ The identification of the inflammatory pathways underlying AD has led to the development and testing of more than 10 broad or targeted therapeutics (Table).⁸ Phase 1 and phase 2 studies of dupilumab (targeting IL-4Rα) have shown not only tremendous AD improvement (~70%) but also tissue reversal of the immune and barrier abnormalities, including inflammatory cytokines and epidermal hyperplasia.^9-11 As a result, other T_H2 axis inhibitors (anti–IL-13/tralokinumab, anti–IL-31RA/CIM 331) are now in clinical trials. The identification of IL-22 in AD lesions has prompted trials with an anti–IL-22 (ILV 094) and an IL-12/IL-23p40 (ustekinumab) inhibitor.¹² For psoriasis, ustekinumab showed 75% improvement in approximately 70% of patients,¹³ but for AD, despite clear clinical and molecular effects, differences compared to placebo were not statistically significant,¹² probably due to underdosing of the drug in an excessively immune-activated disease¹⁴ as well as allowing topical steroids in patients, which may minimize the differences in treatment effect between drug and placebo.

The developments seen in AD are now moving into other inflammatory skin diseases, particularly alopecia areata (AA), a T-cell–mediated disease that shares phenotypic similarities with AD and often is associated with it.¹⁵ There is a paucity of effective, remission-sustaining treatments of AA, particularly for patients with severe disease who rarely experience spontaneous hair regrowth and who have a limited response to topical interventions.^16,17 Our clinical experience showed that successfully treating patients with concurrent AD and AA has led to hair regrowth. Inspired by these clinical observations and by results obtained in AD,^9-12 studying AA skin showed an upregulation of not only the traditionally suspected culprit T_H1 but also T_H2 and T_H9 axes, IL-23 cytokines, and phosphodiesterase 4.¹⁸ Subsequently, a pilot study of 3 patients with extensive AA treated with ustekinumab showed that all 3 patients not only experienced hair regrowth but also had a reduction in inflammatory markers in scalp lesions.¹⁹ Although these results are promising, AA is an immunologically complex disease and it is yet to be determined if therapeutically targeting 1 (eg, IL-4) rather than a wide array of cytokines can reverse disease phenotype. There are ongoing clinical trials directed at different pathogenic targets (eg, Jak inhibitors, IL-13 antagonist, IL-17 antagonist, phosphodiesterase 4 antagonist); some showed some efficacy in small studies.^20,21

The finding of a commonly upregulated T_H2 pathway in both AD and AA will pave the way for studies with T_H2 antagonists in AA patients. Future targeted therapeutic studies will shed light on the pathogenic pathways of this devastating skin disease and answer the extensive unmet therapeutic need it presents.

Atopic dermatitis (AD) is the most common inflammatory skin disease in both adults and children.¹ Unfortunately, the current treatment armamentarium is largely confined to topical calcineurin inhibitors, topical and systemic steroids, phototherapy, cyclosporine (not approved by the US Food and Drug Administration for AD), and other oral immunosuppressants.² The availability of partially helpful and highly toxic treatments creates a huge unmet need for more effective and safer treatments, particularly for patients with moderate to severe AD who often require systemic approaches.

Recent extensive translational (bench top to bedside and back) investigations in skin of AD patients has shown that skin phenotype is characterized by increased T-cell infiltration and related inflammatory cytokines as well as epidermal abnormalities (eg, hyperplasia, aberrant differentiation).³ Clinical improvement of AD has been demonstrated with broad T-cell targeted therapeutics, such as cyclosporine and narrowband UVB, coupled with decreases of T-cell infiltrates and inflammatory gene products as well as improvement of the pathologic epidermal phenotype.^4,5

In the past, AD was conceptualized as a T helper cell T_H2 (acute disease)/T_H1 (chronic disease) bipolar cytokine disorder.⁶ Acute lesions are characterized by high T_H2, T_H22, and some T_H17 signals, with intensification of these axes and T_H1 augmentation orchestrating the chronic phenotype.⁷ The identification of the inflammatory pathways underlying AD has led to the development and testing of more than 10 broad or targeted therapeutics (Table).⁸ Phase 1 and phase 2 studies of dupilumab (targeting IL-4Rα) have shown not only tremendous AD improvement (~70%) but also tissue reversal of the immune and barrier abnormalities, including inflammatory cytokines and epidermal hyperplasia.^9-11 As a result, other T_H2 axis inhibitors (anti–IL-13/tralokinumab, anti–IL-31RA/CIM 331) are now in clinical trials. The identification of IL-22 in AD lesions has prompted trials with an anti–IL-22 (ILV 094) and an IL-12/IL-23p40 (ustekinumab) inhibitor.¹² For psoriasis, ustekinumab showed 75% improvement in approximately 70% of patients,¹³ but for AD, despite clear clinical and molecular effects, differences compared to placebo were not statistically significant,¹² probably due to underdosing of the drug in an excessively immune-activated disease¹⁴ as well as allowing topical steroids in patients, which may minimize the differences in treatment effect between drug and placebo.

The developments seen in AD are now moving into other inflammatory skin diseases, particularly alopecia areata (AA), a T-cell–mediated disease that shares phenotypic similarities with AD and often is associated with it.¹⁵ There is a paucity of effective, remission-sustaining treatments of AA, particularly for patients with severe disease who rarely experience spontaneous hair regrowth and who have a limited response to topical interventions.^16,17 Our clinical experience showed that successfully treating patients with concurrent AD and AA has led to hair regrowth. Inspired by these clinical observations and by results obtained in AD,^9-12 studying AA skin showed an upregulation of not only the traditionally suspected culprit T_H1 but also T_H2 and T_H9 axes, IL-23 cytokines, and phosphodiesterase 4.¹⁸ Subsequently, a pilot study of 3 patients with extensive AA treated with ustekinumab showed that all 3 patients not only experienced hair regrowth but also had a reduction in inflammatory markers in scalp lesions.¹⁹ Although these results are promising, AA is an immunologically complex disease and it is yet to be determined if therapeutically targeting 1 (eg, IL-4) rather than a wide array of cytokines can reverse disease phenotype. There are ongoing clinical trials directed at different pathogenic targets (eg, Jak inhibitors, IL-13 antagonist, IL-17 antagonist, phosphodiesterase 4 antagonist); some showed some efficacy in small studies.^20,21

The finding of a commonly upregulated T_H2 pathway in both AD and AA will pave the way for studies with T_H2 antagonists in AA patients. Future targeted therapeutic studies will shed light on the pathogenic pathways of this devastating skin disease and answer the extensive unmet therapeutic need it presents.

Atopic dermatitis (AD) is the most common inflammatory skin disease in both adults and children.¹ Unfortunately, the current treatment armamentarium is largely confined to topical calcineurin inhibitors, topical and systemic steroids, phototherapy, cyclosporine (not approved by the US Food and Drug Administration for AD), and other oral immunosuppressants.² The availability of partially helpful and highly toxic treatments creates a huge unmet need for more effective and safer treatments, particularly for patients with moderate to severe AD who often require systemic approaches.

Recent extensive translational (bench top to bedside and back) investigations in skin of AD patients has shown that skin phenotype is characterized by increased T-cell infiltration and related inflammatory cytokines as well as epidermal abnormalities (eg, hyperplasia, aberrant differentiation).³ Clinical improvement of AD has been demonstrated with broad T-cell targeted therapeutics, such as cyclosporine and narrowband UVB, coupled with decreases of T-cell infiltrates and inflammatory gene products as well as improvement of the pathologic epidermal phenotype.^4,5

In the past, AD was conceptualized as a T helper cell T_H2 (acute disease)/T_H1 (chronic disease) bipolar cytokine disorder.⁶ Acute lesions are characterized by high T_H2, T_H22, and some T_H17 signals, with intensification of these axes and T_H1 augmentation orchestrating the chronic phenotype.⁷ The identification of the inflammatory pathways underlying AD has led to the development and testing of more than 10 broad or targeted therapeutics (Table).⁸ Phase 1 and phase 2 studies of dupilumab (targeting IL-4Rα) have shown not only tremendous AD improvement (~70%) but also tissue reversal of the immune and barrier abnormalities, including inflammatory cytokines and epidermal hyperplasia.^9-11 As a result, other T_H2 axis inhibitors (anti–IL-13/tralokinumab, anti–IL-31RA/CIM 331) are now in clinical trials. The identification of IL-22 in AD lesions has prompted trials with an anti–IL-22 (ILV 094) and an IL-12/IL-23p40 (ustekinumab) inhibitor.¹² For psoriasis, ustekinumab showed 75% improvement in approximately 70% of patients,¹³ but for AD, despite clear clinical and molecular effects, differences compared to placebo were not statistically significant,¹² probably due to underdosing of the drug in an excessively immune-activated disease¹⁴ as well as allowing topical steroids in patients, which may minimize the differences in treatment effect between drug and placebo.

The developments seen in AD are now moving into other inflammatory skin diseases, particularly alopecia areata (AA), a T-cell–mediated disease that shares phenotypic similarities with AD and often is associated with it.¹⁵ There is a paucity of effective, remission-sustaining treatments of AA, particularly for patients with severe disease who rarely experience spontaneous hair regrowth and who have a limited response to topical interventions.^16,17 Our clinical experience showed that successfully treating patients with concurrent AD and AA has led to hair regrowth. Inspired by these clinical observations and by results obtained in AD,^9-12 studying AA skin showed an upregulation of not only the traditionally suspected culprit T_H1 but also T_H2 and T_H9 axes, IL-23 cytokines, and phosphodiesterase 4.¹⁸ Subsequently, a pilot study of 3 patients with extensive AA treated with ustekinumab showed that all 3 patients not only experienced hair regrowth but also had a reduction in inflammatory markers in scalp lesions.¹⁹ Although these results are promising, AA is an immunologically complex disease and it is yet to be determined if therapeutically targeting 1 (eg, IL-4) rather than a wide array of cytokines can reverse disease phenotype. There are ongoing clinical trials directed at different pathogenic targets (eg, Jak inhibitors, IL-13 antagonist, IL-17 antagonist, phosphodiesterase 4 antagonist); some showed some efficacy in small studies.^20,21

The finding of a commonly upregulated T_H2 pathway in both AD and AA will pave the way for studies with T_H2 antagonists in AA patients. Future targeted therapeutic studies will shed light on the pathogenic pathways of this devastating skin disease and answer the extensive unmet therapeutic need it presents.

In most high-income countries, including the US, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² In the absence of a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the CDC began recommending daily use of tenofovir, disoproxil, fumarate, and emtricitabine (TDF-FTC) in high-risk individuals as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT], 46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably due to the difficulty in getting patients to take the medication daily.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ This is because, until now, no studies had demonstrated the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays study—a double-blind, multicenter study conducted in France and Canada—assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis proposed that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk for HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection—defined as having a history of unprotected anal sex with at least two partners in the past six months. Other inclusion criteria included an age of at least 18 and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance < 60 mL/min, alanine aminotransferase level more than 2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. Those who withdrew consent, were lost to follow-up, or acquired HIV-1 infection were excluded, and the remaining study participants were randomized to take TDF-FTC (n = 199) or placebo (n = 201) before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. Participants were instructed to take a loading dose of two pills of TDF-FTC or placebo with food two to 24 hours prior to intercourse, a third pill 24 hours later, and a fourth pill 24 hours after the third.

If there were multiple consecutive days of sexual intercourse, participants were to take one pill on each day of intercourse, followed by the two postexposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the PrEP; otherwise, they were to begin again with two pills two to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants four and eight weeks after enrollment, then every eight weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count, drug levels in plasma, and with an at-home, computer-assisted interview completed by participants prior to each visit.

Participants received counseling from a peer community member and were offered preventive services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took their assigned pills correctly. Participants were followed for a median of 9.3 months. Overall, 72% of participants took the study drugs (TDF-FTC or placebo), but 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. After 20 months, the study was unblinded and is now continuing as an open-label study because of the discontinuation of another PrEP study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk for HIV without PrEP. The open-label part of the study (iPrex-OLE) completed enrollment and data gathering in November 2013. The data analysis and results are pending.⁹

Eighty-six percent experienced relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with three of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group and two of the new cases were in the TDF-FTC group. This translated to an 86% relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group (NNT, 17 over 9.3 months).

The two cases in the TDF-FTC group occurred in participants found to be nonadherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain, which were seen more commonly in the treatment group than in the placebo group (14% vs 5%; number needed to harm, 11). There were also mild increases in serum creatinine level, but only two participants had a transient decrease in creatinine clearance to < 60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction nearly doubles

This is the first study to look at on-demand PrEP with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the increased benefit of on-demand PrEP is likely due to improved compliance with medication use.

CAVEATS

Can adherence be maintained?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we need to wait for the results of the open-label study to fully assess the risk for adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of the medication; the retail price of TDF-FTC is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

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 © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(8):556-558.

In most high-income countries, including the US, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² In the absence of a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the CDC began recommending daily use of tenofovir, disoproxil, fumarate, and emtricitabine (TDF-FTC) in high-risk individuals as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT], 46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably due to the difficulty in getting patients to take the medication daily.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ This is because, until now, no studies had demonstrated the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays study—a double-blind, multicenter study conducted in France and Canada—assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis proposed that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk for HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection—defined as having a history of unprotected anal sex with at least two partners in the past six months. Other inclusion criteria included an age of at least 18 and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance < 60 mL/min, alanine aminotransferase level more than 2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. Those who withdrew consent, were lost to follow-up, or acquired HIV-1 infection were excluded, and the remaining study participants were randomized to take TDF-FTC (n = 199) or placebo (n = 201) before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. Participants were instructed to take a loading dose of two pills of TDF-FTC or placebo with food two to 24 hours prior to intercourse, a third pill 24 hours later, and a fourth pill 24 hours after the third.

If there were multiple consecutive days of sexual intercourse, participants were to take one pill on each day of intercourse, followed by the two postexposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the PrEP; otherwise, they were to begin again with two pills two to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants four and eight weeks after enrollment, then every eight weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count, drug levels in plasma, and with an at-home, computer-assisted interview completed by participants prior to each visit.

Participants received counseling from a peer community member and were offered preventive services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took their assigned pills correctly. Participants were followed for a median of 9.3 months. Overall, 72% of participants took the study drugs (TDF-FTC or placebo), but 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. After 20 months, the study was unblinded and is now continuing as an open-label study because of the discontinuation of another PrEP study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk for HIV without PrEP. The open-label part of the study (iPrex-OLE) completed enrollment and data gathering in November 2013. The data analysis and results are pending.⁹

Eighty-six percent experienced relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with three of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group and two of the new cases were in the TDF-FTC group. This translated to an 86% relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group (NNT, 17 over 9.3 months).

The two cases in the TDF-FTC group occurred in participants found to be nonadherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain, which were seen more commonly in the treatment group than in the placebo group (14% vs 5%; number needed to harm, 11). There were also mild increases in serum creatinine level, but only two participants had a transient decrease in creatinine clearance to < 60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction nearly doubles

This is the first study to look at on-demand PrEP with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the increased benefit of on-demand PrEP is likely due to improved compliance with medication use.

CAVEATS

Can adherence be maintained?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we need to wait for the results of the open-label study to fully assess the risk for adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of the medication; the retail price of TDF-FTC is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

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 © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(8):556-558.

In most high-income countries, including the US, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² In the absence of a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the CDC began recommending daily use of tenofovir, disoproxil, fumarate, and emtricitabine (TDF-FTC) in high-risk individuals as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT], 46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably due to the difficulty in getting patients to take the medication daily.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ This is because, until now, no studies had demonstrated the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays study—a double-blind, multicenter study conducted in France and Canada—assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis proposed that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk for HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection—defined as having a history of unprotected anal sex with at least two partners in the past six months. Other inclusion criteria included an age of at least 18 and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance < 60 mL/min, alanine aminotransferase level more than 2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. Those who withdrew consent, were lost to follow-up, or acquired HIV-1 infection were excluded, and the remaining study participants were randomized to take TDF-FTC (n = 199) or placebo (n = 201) before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. Participants were instructed to take a loading dose of two pills of TDF-FTC or placebo with food two to 24 hours prior to intercourse, a third pill 24 hours later, and a fourth pill 24 hours after the third.

If there were multiple consecutive days of sexual intercourse, participants were to take one pill on each day of intercourse, followed by the two postexposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the PrEP; otherwise, they were to begin again with two pills two to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants four and eight weeks after enrollment, then every eight weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count, drug levels in plasma, and with an at-home, computer-assisted interview completed by participants prior to each visit.

Participants received counseling from a peer community member and were offered preventive services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took their assigned pills correctly. Participants were followed for a median of 9.3 months. Overall, 72% of participants took the study drugs (TDF-FTC or placebo), but 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. After 20 months, the study was unblinded and is now continuing as an open-label study because of the discontinuation of another PrEP study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk for HIV without PrEP. The open-label part of the study (iPrex-OLE) completed enrollment and data gathering in November 2013. The data analysis and results are pending.⁹

Eighty-six percent experienced relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with three of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group and two of the new cases were in the TDF-FTC group. This translated to an 86% relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group (NNT, 17 over 9.3 months).

The two cases in the TDF-FTC group occurred in participants found to be nonadherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain, which were seen more commonly in the treatment group than in the placebo group (14% vs 5%; number needed to harm, 11). There were also mild increases in serum creatinine level, but only two participants had a transient decrease in creatinine clearance to < 60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction nearly doubles

This is the first study to look at on-demand PrEP with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the increased benefit of on-demand PrEP is likely due to improved compliance with medication use.

CAVEATS

Can adherence be maintained?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we need to wait for the results of the open-label study to fully assess the risk for adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of the medication; the retail price of TDF-FTC is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

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 © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(8):556-558.

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

[email protected]

On Twitter @jessnicolecraig

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

[email protected]

On Twitter @jessnicolecraig

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

[email protected]

On Twitter @jessnicolecraig

Going to medical school at Universidad Autónoma de Guadalajara in Guadalajara, Mexico, could have been too much for Benjamin Frizner, MD, FHM.

Medicine is its own new language, as any first-year can tell you. Throw in learning Spanish? And a new culture? One could be forgiven for not excelling.

Dr. Frizner isn’t one of those people.

“The experience changed my life,” he says. “After I survived the first year, I knew I loved medicine.”

After medical school, Dr. Frizner had to complete a Fifth Pathway program, which formerly allowed students who completed four years at a foreign medical school to finish supervised clinical work at a U.S. medical school and become eligible as a U.S. resident.

He learned of hospital medicine during his residency at York Hospital in York, Pa., and, despite others suggesting hospital medicine was “something to do before you really figure out your career,” he enjoyed both working within the hospital walls and having a schedule that allowed 15 shifts a month and commensurate time off.

But as with his shift from undergraduate school in suburban Maryland to medical school in Mexico, Dr. Frizner likes a new challenge. So after a four-year stint as director of the hospitalist program at Saint Agnes Hospital in Baltimore, he took a job in August 2015 as director of the Ventilator Unit at FutureCare Irvington, a post-acute-care center in Baltimore staffed by CEP America.

“Post-acute care has become a new passion and chapter in my career,” he says, adding, “Skilled nursing facilities are extensions of the acute-care hospital and are just as challenging and fulfilling as hospitalist work.”

It’s a perspective Dr. Frizner will bring as one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Why did you choose a career in medicine?

Answer: I enjoyed math and biology in college. I started out thinking I would be an engineer but fell in love with anatomy. I like solving problems and working with people. Internal medicine/hospital medicine is a perfect match, working to solve a patient’s diagnosis and helping families make difficult decisions about placement and palliative care.

Q: What do you like most about working as a hospitalist?

A: Interacting with all the different specialties, social work, case management, residents, ED docs. I really enjoy the camaraderie.

Q: What do you dislike most?

A: Hospital groups contribute immensely to patient flow, care, quality, process improvement, throughput, but hospitals always advertise the new specialist and never the excellent hospitalist group.

Q: What’s the best advice you ever received?

A: No matter what, do what is best for the patient. Everything else will take care of itself.

Q: What’s the worst advice you ever received?

A: Don’t worry about the contract; you don’t need to really look it over.

Q: What’s the biggest change you’ve seen in HM in your career?

A: The pace of medicine continues to speed up. Residents have to hit the ground running with baseline case-management knowledge.

Q: What’s the biggest change you would like to see in HM?

A: I would like to see more hospitalists ascend into senior leadership in hospitals and healthcare systems.

Q: Why should group leaders continue to see patients?

A: It is important to maintain trust and respect with docs you are leading and managing. When I was a hospitalist director, I made sure I worked nights and weekends so I could understand the workload during those shifts and my team felt I was not just dumping on them.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Establishing trust with the patient and their family. But it has become second nature to me at this point. The secret is to introduce yourself, tell the patient and family you will take care of them in the hospital, communicate with their outpatient physician and that you are part of a 24-7 team of docs there to take care of the patient.

Q: What aspect of patient care is most rewarding?

A: Helping families navigate end-of-life decisions. It is the most stressful time in a family’s life, and I think it is the most rewarding and honorable part of practicing medicine.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I lead teaching rounds a few months a year when I was a hospitalist director, and I think the most difficult part is getting the residents to understand the workload will be a lot tougher when they get out into the real world. During their third year, residents need to practice efficiency and gauge their work ethic—not the kind of work ethic needed to pass the boards but the kind needed to stay in the ED and help your teammate out until the admissions are caught up or round on a few extra patients when there is a surge in the census.

Q: What is your biggest professional challenge?

A: [Getting others to] stop underestimating my skills and experience as a hospitalist and physician leader. I will complete an MBA through ACPE UMass this December. Learning basic accounting, business law, and finance has helped round out blind spots and build my confidence.

Q: What is your biggest professional reward?

A: Completing quality improvement projects such as increasing DVT prophylaxis, reducing CAUTI, and decreasing throughput times, which all help make the hospital course safer and efficient for the patient.

Q: What SHM event made the most lasting impression on you?

A: Seven years ago, I attended the Level I leadership academy at the Aria hotel in Las Vegas. The meeting opened my eyes to the world of leadership, management, and healthcare economics, which sparked my drive to eventually become a hospitalist director.

Q: What’s the best book you’ve read recently? Why?

A: David and Goliath by Malcolm Gladwell. As a foreign medical graduate, I was told there would be limits to what I could achieve in my career. Mr. Gladwell’s book is filled with stories of people who overcame difficult situations and went on to rise to the top of their fields.

Richard Quinn is a freelance writer in New Jersey.

Going to medical school at Universidad Autónoma de Guadalajara in Guadalajara, Mexico, could have been too much for Benjamin Frizner, MD, FHM.

Medicine is its own new language, as any first-year can tell you. Throw in learning Spanish? And a new culture? One could be forgiven for not excelling.

Dr. Frizner isn’t one of those people.

“The experience changed my life,” he says. “After I survived the first year, I knew I loved medicine.”

After medical school, Dr. Frizner had to complete a Fifth Pathway program, which formerly allowed students who completed four years at a foreign medical school to finish supervised clinical work at a U.S. medical school and become eligible as a U.S. resident.

He learned of hospital medicine during his residency at York Hospital in York, Pa., and, despite others suggesting hospital medicine was “something to do before you really figure out your career,” he enjoyed both working within the hospital walls and having a schedule that allowed 15 shifts a month and commensurate time off.

But as with his shift from undergraduate school in suburban Maryland to medical school in Mexico, Dr. Frizner likes a new challenge. So after a four-year stint as director of the hospitalist program at Saint Agnes Hospital in Baltimore, he took a job in August 2015 as director of the Ventilator Unit at FutureCare Irvington, a post-acute-care center in Baltimore staffed by CEP America.

“Post-acute care has become a new passion and chapter in my career,” he says, adding, “Skilled nursing facilities are extensions of the acute-care hospital and are just as challenging and fulfilling as hospitalist work.”

It’s a perspective Dr. Frizner will bring as one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Why did you choose a career in medicine?

Answer: I enjoyed math and biology in college. I started out thinking I would be an engineer but fell in love with anatomy. I like solving problems and working with people. Internal medicine/hospital medicine is a perfect match, working to solve a patient’s diagnosis and helping families make difficult decisions about placement and palliative care.

Q: What do you like most about working as a hospitalist?

A: Interacting with all the different specialties, social work, case management, residents, ED docs. I really enjoy the camaraderie.

Q: What do you dislike most?

A: Hospital groups contribute immensely to patient flow, care, quality, process improvement, throughput, but hospitals always advertise the new specialist and never the excellent hospitalist group.

Q: What’s the best advice you ever received?

A: No matter what, do what is best for the patient. Everything else will take care of itself.

Q: What’s the worst advice you ever received?

A: Don’t worry about the contract; you don’t need to really look it over.

Q: What’s the biggest change you’ve seen in HM in your career?

A: The pace of medicine continues to speed up. Residents have to hit the ground running with baseline case-management knowledge.

Q: What’s the biggest change you would like to see in HM?

A: I would like to see more hospitalists ascend into senior leadership in hospitals and healthcare systems.

Q: Why should group leaders continue to see patients?

A: It is important to maintain trust and respect with docs you are leading and managing. When I was a hospitalist director, I made sure I worked nights and weekends so I could understand the workload during those shifts and my team felt I was not just dumping on them.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Establishing trust with the patient and their family. But it has become second nature to me at this point. The secret is to introduce yourself, tell the patient and family you will take care of them in the hospital, communicate with their outpatient physician and that you are part of a 24-7 team of docs there to take care of the patient.

Q: What aspect of patient care is most rewarding?

A: Helping families navigate end-of-life decisions. It is the most stressful time in a family’s life, and I think it is the most rewarding and honorable part of practicing medicine.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I lead teaching rounds a few months a year when I was a hospitalist director, and I think the most difficult part is getting the residents to understand the workload will be a lot tougher when they get out into the real world. During their third year, residents need to practice efficiency and gauge their work ethic—not the kind of work ethic needed to pass the boards but the kind needed to stay in the ED and help your teammate out until the admissions are caught up or round on a few extra patients when there is a surge in the census.

Q: What is your biggest professional challenge?

A: [Getting others to] stop underestimating my skills and experience as a hospitalist and physician leader. I will complete an MBA through ACPE UMass this December. Learning basic accounting, business law, and finance has helped round out blind spots and build my confidence.

Q: What is your biggest professional reward?

A: Completing quality improvement projects such as increasing DVT prophylaxis, reducing CAUTI, and decreasing throughput times, which all help make the hospital course safer and efficient for the patient.

Q: What SHM event made the most lasting impression on you?

A: Seven years ago, I attended the Level I leadership academy at the Aria hotel in Las Vegas. The meeting opened my eyes to the world of leadership, management, and healthcare economics, which sparked my drive to eventually become a hospitalist director.

Q: What’s the best book you’ve read recently? Why?

A: David and Goliath by Malcolm Gladwell. As a foreign medical graduate, I was told there would be limits to what I could achieve in my career. Mr. Gladwell’s book is filled with stories of people who overcame difficult situations and went on to rise to the top of their fields.

Richard Quinn is a freelance writer in New Jersey.

Going to medical school at Universidad Autónoma de Guadalajara in Guadalajara, Mexico, could have been too much for Benjamin Frizner, MD, FHM.

Medicine is its own new language, as any first-year can tell you. Throw in learning Spanish? And a new culture? One could be forgiven for not excelling.

Dr. Frizner isn’t one of those people.

“The experience changed my life,” he says. “After I survived the first year, I knew I loved medicine.”

After medical school, Dr. Frizner had to complete a Fifth Pathway program, which formerly allowed students who completed four years at a foreign medical school to finish supervised clinical work at a U.S. medical school and become eligible as a U.S. resident.

He learned of hospital medicine during his residency at York Hospital in York, Pa., and, despite others suggesting hospital medicine was “something to do before you really figure out your career,” he enjoyed both working within the hospital walls and having a schedule that allowed 15 shifts a month and commensurate time off.

But as with his shift from undergraduate school in suburban Maryland to medical school in Mexico, Dr. Frizner likes a new challenge. So after a four-year stint as director of the hospitalist program at Saint Agnes Hospital in Baltimore, he took a job in August 2015 as director of the Ventilator Unit at FutureCare Irvington, a post-acute-care center in Baltimore staffed by CEP America.

“Post-acute care has become a new passion and chapter in my career,” he says, adding, “Skilled nursing facilities are extensions of the acute-care hospital and are just as challenging and fulfilling as hospitalist work.”

It’s a perspective Dr. Frizner will bring as one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Why did you choose a career in medicine?

Answer: I enjoyed math and biology in college. I started out thinking I would be an engineer but fell in love with anatomy. I like solving problems and working with people. Internal medicine/hospital medicine is a perfect match, working to solve a patient’s diagnosis and helping families make difficult decisions about placement and palliative care.

Q: What do you like most about working as a hospitalist?

A: Interacting with all the different specialties, social work, case management, residents, ED docs. I really enjoy the camaraderie.

Q: What do you dislike most?

A: Hospital groups contribute immensely to patient flow, care, quality, process improvement, throughput, but hospitals always advertise the new specialist and never the excellent hospitalist group.

Q: What’s the best advice you ever received?

A: No matter what, do what is best for the patient. Everything else will take care of itself.

Q: What’s the worst advice you ever received?

A: Don’t worry about the contract; you don’t need to really look it over.

Q: What’s the biggest change you’ve seen in HM in your career?

A: The pace of medicine continues to speed up. Residents have to hit the ground running with baseline case-management knowledge.

Q: What’s the biggest change you would like to see in HM?

A: I would like to see more hospitalists ascend into senior leadership in hospitals and healthcare systems.

Q: Why should group leaders continue to see patients?

A: It is important to maintain trust and respect with docs you are leading and managing. When I was a hospitalist director, I made sure I worked nights and weekends so I could understand the workload during those shifts and my team felt I was not just dumping on them.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Establishing trust with the patient and their family. But it has become second nature to me at this point. The secret is to introduce yourself, tell the patient and family you will take care of them in the hospital, communicate with their outpatient physician and that you are part of a 24-7 team of docs there to take care of the patient.

Q: What aspect of patient care is most rewarding?

A: Helping families navigate end-of-life decisions. It is the most stressful time in a family’s life, and I think it is the most rewarding and honorable part of practicing medicine.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I lead teaching rounds a few months a year when I was a hospitalist director, and I think the most difficult part is getting the residents to understand the workload will be a lot tougher when they get out into the real world. During their third year, residents need to practice efficiency and gauge their work ethic—not the kind of work ethic needed to pass the boards but the kind needed to stay in the ED and help your teammate out until the admissions are caught up or round on a few extra patients when there is a surge in the census.

Q: What is your biggest professional challenge?

A: [Getting others to] stop underestimating my skills and experience as a hospitalist and physician leader. I will complete an MBA through ACPE UMass this December. Learning basic accounting, business law, and finance has helped round out blind spots and build my confidence.

Q: What is your biggest professional reward?

A: Completing quality improvement projects such as increasing DVT prophylaxis, reducing CAUTI, and decreasing throughput times, which all help make the hospital course safer and efficient for the patient.

Q: What SHM event made the most lasting impression on you?

A: Seven years ago, I attended the Level I leadership academy at the Aria hotel in Las Vegas. The meeting opened my eyes to the world of leadership, management, and healthcare economics, which sparked my drive to eventually become a hospitalist director.

Q: What’s the best book you’ve read recently? Why?

A: David and Goliath by Malcolm Gladwell. As a foreign medical graduate, I was told there would be limits to what I could achieve in my career. Mr. Gladwell’s book is filled with stories of people who overcame difficult situations and went on to rise to the top of their fields.

Richard Quinn is a freelance writer in New Jersey.