Not much intimidates Jasen Gundersen, MD, president of the acute care services division at TeamHealth, an outsourcer of hospital-based clinical and specialty services based in Knoxville, Tenn. Besides traveling 150,000 miles a year overseeing 2,500 hospitalists at 285 facilities, Dr. Gundersen has climbed frozen waterfalls in Vermont and New Hampshire, raced in bicycle competitions, and skied mountains towering 10,000 feet.

But his love for adventure is now focused below the surface. Over the years, he has spent many weekends diving in open waters surrounding southeast Florida; Cozumel, Mexico; Turks and Caicos; and the Cayman Islands. He believes there’s no place on Earth that is as peaceful, serene, or even magical as under the ocean.

Reclaimed Passion

Growing up in Connecticut, Dr. Gundersen and his family frequently vacationed in the Bahamas, where he was introduced to scuba diving.

“As a teenager, I really loved diving,” he recalls. “Every time we went to the Bahamas, I always tried to go diving or snorkeling.”

However, the harsh Connecticut winters and frigid Atlantic Ocean prevented him from diving. More delays followed, namely medical school. After graduating from the University of Connecticut School of Medicine in 2000, Dr. Gundersen completed his three-year residency in family medicine at the UMass Memorial Medical Center. During the next two years, he worked as a physician and hospitalist at the Family Health Center of Worcester, a federally qualified health center where he did everything from examining sore throats to delivering babies.

In 2005, he launched a small hospital medicine program at the University of Massachusetts that quickly grew and bumped up his title to division chief for hospital medicine. Then in January 2011, he accepted a new position as chief medical officer at TeamHealth, requiring him and his wife, Elizabeth, also a hospitalist, to move to Florida.

Within several weeks, the couple started diving near their home in Pompano Beach. He says Elizabeth, his “diving buddy,” was eager to learn and developed a passion for scuba diving that rivals his own.

“We did 80 to 90 dives in the first year we were down there,” Dr. Gundersen says, explaining that unlike many sports, diving doesn’t require athletic ability, size, or strength. “We normally did recreational diving, where you basically can always swim slowly straight to the surface. You don’t stay down long enough that you build up enough bubbles in your system that you have to stop on the way up.”

Sharks and Shipwrecks

Since then, Dr. Gundersen purchased a 38-foot powerboat, became a PADI (Professional Association of Diving Instructors) open-water scuba instructor, and earned a U.S. Coast Guard 50-ton master captain’s license. He and Elizabeth are certified for advanced nitrox and decompression diving, technical diving that requires the use of different gases to decompress when heading to the surface, and diving in overhead environments, such as caves or shipwrecks.

“One of our favorite wrecks is called the USS Spiegel Gove that sits on the ocean floor in Key Largo,” he says, adding that on occasion, they also swim with hammerhead sharks. “The walls of the ship go 30 feet up on each side. You can swim where they loaded the cargo and see the old crane above you. It’s spectacular.”

Among their favorite spots to dive is Eagle Ray Pass in Grand Cayman, where entire schools of spotted eagle rays live, he says, adding that 17 rays swam and floated around them during one dive.

Fortunately, after some initial costs, he says the sport isn’t too expensive, roughly around $1,500 to get started. Basic scuba gear costs approximately $1,000. Likewise, certifications can run $350 a piece. Boat trips range between $60 and $100, unless you prefer shore diving, where you park at the beach and simply swim into the ocean. Then add a few extra dollars to fill your tank with air.

Scary and Serene

Although the Gundersens are accomplished divers who prefer warm waters and flat seas, Dr. Gundersen says only one moment of one dive actually scared him.

Years ago, he, Elizabeth, and a friend were wreck diving. Diving protocol is based on follow the leader, where divers swim into wrecks one at a time, follow each other, and signal their turns. Somehow, their friend unintentionally swam in between Dr. Gundersen and his wife. Elizabeth and the friend then turned to see something inside the wreck, but the friend failed to signal to Dr. Gundersen that they were turning.

“I went a bit farther and turned around,” Dr. Gundersen recalls. “He and Elizabeth were gone. It gave me a moment of panic. I’m particularly careful about staying with my diving buddy and making sure we don’t get lost. It wasn’t dangerous but broke the cardinal rule of what you’re supposed to do when diving. I swam back and found them.”

While that was a rare experience, he says diving, when done properly, is the most peaceful and serene activity that people may experience. When under water, all you hear are your air bubbles. There are no cellphones ringing, emails or texts to respond to, or work issues to resolve.

“Work-life balance is a really big deal for me and my team to prevent burnout,” Dr. Gundersen says. “It allows me to have my personal time to enjoy and relax so when I’m back at work on Monday, my batteries are recharged. I’m ready to go.” TH

Carol Patton is a freelance writer in Las Vegas.

Not much intimidates Jasen Gundersen, MD, president of the acute care services division at TeamHealth, an outsourcer of hospital-based clinical and specialty services based in Knoxville, Tenn. Besides traveling 150,000 miles a year overseeing 2,500 hospitalists at 285 facilities, Dr. Gundersen has climbed frozen waterfalls in Vermont and New Hampshire, raced in bicycle competitions, and skied mountains towering 10,000 feet.

But his love for adventure is now focused below the surface. Over the years, he has spent many weekends diving in open waters surrounding southeast Florida; Cozumel, Mexico; Turks and Caicos; and the Cayman Islands. He believes there’s no place on Earth that is as peaceful, serene, or even magical as under the ocean.

Reclaimed Passion

Growing up in Connecticut, Dr. Gundersen and his family frequently vacationed in the Bahamas, where he was introduced to scuba diving.

“As a teenager, I really loved diving,” he recalls. “Every time we went to the Bahamas, I always tried to go diving or snorkeling.”

However, the harsh Connecticut winters and frigid Atlantic Ocean prevented him from diving. More delays followed, namely medical school. After graduating from the University of Connecticut School of Medicine in 2000, Dr. Gundersen completed his three-year residency in family medicine at the UMass Memorial Medical Center. During the next two years, he worked as a physician and hospitalist at the Family Health Center of Worcester, a federally qualified health center where he did everything from examining sore throats to delivering babies.

In 2005, he launched a small hospital medicine program at the University of Massachusetts that quickly grew and bumped up his title to division chief for hospital medicine. Then in January 2011, he accepted a new position as chief medical officer at TeamHealth, requiring him and his wife, Elizabeth, also a hospitalist, to move to Florida.

Within several weeks, the couple started diving near their home in Pompano Beach. He says Elizabeth, his “diving buddy,” was eager to learn and developed a passion for scuba diving that rivals his own.

“We did 80 to 90 dives in the first year we were down there,” Dr. Gundersen says, explaining that unlike many sports, diving doesn’t require athletic ability, size, or strength. “We normally did recreational diving, where you basically can always swim slowly straight to the surface. You don’t stay down long enough that you build up enough bubbles in your system that you have to stop on the way up.”

Sharks and Shipwrecks

Since then, Dr. Gundersen purchased a 38-foot powerboat, became a PADI (Professional Association of Diving Instructors) open-water scuba instructor, and earned a U.S. Coast Guard 50-ton master captain’s license. He and Elizabeth are certified for advanced nitrox and decompression diving, technical diving that requires the use of different gases to decompress when heading to the surface, and diving in overhead environments, such as caves or shipwrecks.

“One of our favorite wrecks is called the USS Spiegel Gove that sits on the ocean floor in Key Largo,” he says, adding that on occasion, they also swim with hammerhead sharks. “The walls of the ship go 30 feet up on each side. You can swim where they loaded the cargo and see the old crane above you. It’s spectacular.”

Among their favorite spots to dive is Eagle Ray Pass in Grand Cayman, where entire schools of spotted eagle rays live, he says, adding that 17 rays swam and floated around them during one dive.

Fortunately, after some initial costs, he says the sport isn’t too expensive, roughly around $1,500 to get started. Basic scuba gear costs approximately $1,000. Likewise, certifications can run $350 a piece. Boat trips range between $60 and $100, unless you prefer shore diving, where you park at the beach and simply swim into the ocean. Then add a few extra dollars to fill your tank with air.

Scary and Serene

Although the Gundersens are accomplished divers who prefer warm waters and flat seas, Dr. Gundersen says only one moment of one dive actually scared him.

Years ago, he, Elizabeth, and a friend were wreck diving. Diving protocol is based on follow the leader, where divers swim into wrecks one at a time, follow each other, and signal their turns. Somehow, their friend unintentionally swam in between Dr. Gundersen and his wife. Elizabeth and the friend then turned to see something inside the wreck, but the friend failed to signal to Dr. Gundersen that they were turning.

“I went a bit farther and turned around,” Dr. Gundersen recalls. “He and Elizabeth were gone. It gave me a moment of panic. I’m particularly careful about staying with my diving buddy and making sure we don’t get lost. It wasn’t dangerous but broke the cardinal rule of what you’re supposed to do when diving. I swam back and found them.”

While that was a rare experience, he says diving, when done properly, is the most peaceful and serene activity that people may experience. When under water, all you hear are your air bubbles. There are no cellphones ringing, emails or texts to respond to, or work issues to resolve.

“Work-life balance is a really big deal for me and my team to prevent burnout,” Dr. Gundersen says. “It allows me to have my personal time to enjoy and relax so when I’m back at work on Monday, my batteries are recharged. I’m ready to go.” TH

Carol Patton is a freelance writer in Las Vegas.

Not much intimidates Jasen Gundersen, MD, president of the acute care services division at TeamHealth, an outsourcer of hospital-based clinical and specialty services based in Knoxville, Tenn. Besides traveling 150,000 miles a year overseeing 2,500 hospitalists at 285 facilities, Dr. Gundersen has climbed frozen waterfalls in Vermont and New Hampshire, raced in bicycle competitions, and skied mountains towering 10,000 feet.

But his love for adventure is now focused below the surface. Over the years, he has spent many weekends diving in open waters surrounding southeast Florida; Cozumel, Mexico; Turks and Caicos; and the Cayman Islands. He believes there’s no place on Earth that is as peaceful, serene, or even magical as under the ocean.

Reclaimed Passion

Growing up in Connecticut, Dr. Gundersen and his family frequently vacationed in the Bahamas, where he was introduced to scuba diving.

“As a teenager, I really loved diving,” he recalls. “Every time we went to the Bahamas, I always tried to go diving or snorkeling.”

However, the harsh Connecticut winters and frigid Atlantic Ocean prevented him from diving. More delays followed, namely medical school. After graduating from the University of Connecticut School of Medicine in 2000, Dr. Gundersen completed his three-year residency in family medicine at the UMass Memorial Medical Center. During the next two years, he worked as a physician and hospitalist at the Family Health Center of Worcester, a federally qualified health center where he did everything from examining sore throats to delivering babies.

In 2005, he launched a small hospital medicine program at the University of Massachusetts that quickly grew and bumped up his title to division chief for hospital medicine. Then in January 2011, he accepted a new position as chief medical officer at TeamHealth, requiring him and his wife, Elizabeth, also a hospitalist, to move to Florida.

Within several weeks, the couple started diving near their home in Pompano Beach. He says Elizabeth, his “diving buddy,” was eager to learn and developed a passion for scuba diving that rivals his own.

“We did 80 to 90 dives in the first year we were down there,” Dr. Gundersen says, explaining that unlike many sports, diving doesn’t require athletic ability, size, or strength. “We normally did recreational diving, where you basically can always swim slowly straight to the surface. You don’t stay down long enough that you build up enough bubbles in your system that you have to stop on the way up.”

Sharks and Shipwrecks

Since then, Dr. Gundersen purchased a 38-foot powerboat, became a PADI (Professional Association of Diving Instructors) open-water scuba instructor, and earned a U.S. Coast Guard 50-ton master captain’s license. He and Elizabeth are certified for advanced nitrox and decompression diving, technical diving that requires the use of different gases to decompress when heading to the surface, and diving in overhead environments, such as caves or shipwrecks.

“One of our favorite wrecks is called the USS Spiegel Gove that sits on the ocean floor in Key Largo,” he says, adding that on occasion, they also swim with hammerhead sharks. “The walls of the ship go 30 feet up on each side. You can swim where they loaded the cargo and see the old crane above you. It’s spectacular.”

Among their favorite spots to dive is Eagle Ray Pass in Grand Cayman, where entire schools of spotted eagle rays live, he says, adding that 17 rays swam and floated around them during one dive.

Fortunately, after some initial costs, he says the sport isn’t too expensive, roughly around $1,500 to get started. Basic scuba gear costs approximately $1,000. Likewise, certifications can run $350 a piece. Boat trips range between $60 and $100, unless you prefer shore diving, where you park at the beach and simply swim into the ocean. Then add a few extra dollars to fill your tank with air.

Scary and Serene

Although the Gundersens are accomplished divers who prefer warm waters and flat seas, Dr. Gundersen says only one moment of one dive actually scared him.

Years ago, he, Elizabeth, and a friend were wreck diving. Diving protocol is based on follow the leader, where divers swim into wrecks one at a time, follow each other, and signal their turns. Somehow, their friend unintentionally swam in between Dr. Gundersen and his wife. Elizabeth and the friend then turned to see something inside the wreck, but the friend failed to signal to Dr. Gundersen that they were turning.

“I went a bit farther and turned around,” Dr. Gundersen recalls. “He and Elizabeth were gone. It gave me a moment of panic. I’m particularly careful about staying with my diving buddy and making sure we don’t get lost. It wasn’t dangerous but broke the cardinal rule of what you’re supposed to do when diving. I swam back and found them.”

While that was a rare experience, he says diving, when done properly, is the most peaceful and serene activity that people may experience. When under water, all you hear are your air bubbles. There are no cellphones ringing, emails or texts to respond to, or work issues to resolve.

“Work-life balance is a really big deal for me and my team to prevent burnout,” Dr. Gundersen says. “It allows me to have my personal time to enjoy and relax so when I’m back at work on Monday, my batteries are recharged. I’m ready to go.” TH

Carol Patton is a freelance writer in Las Vegas.

Click here to access the May 2016 Digital Edition. 

Table of Contents

• Why VA Health Care Is Different
• Anterior Cervical Interbody Fusion Using Polyetheretherketone (PEEK) Cage Device and Local Autograft Bone
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 2
• A Real Welcome Home: Permanent Housing for Homeless Veterans
• Veterans’ Satisfaction With Erectile Dysfunction Treatment
• VA PBM Academic Detailing Service: Implementation and Lessons Learned
• Adherence to Disease-Modifying Therapies in Patients With MS: A Retrospective Cohort Study
• The Role of Fidaxomicin in Clostridium difficile Infection

Click here to access the May 2016 Digital Edition. 

Table of Contents

• Why VA Health Care Is Different
• Anterior Cervical Interbody Fusion Using Polyetheretherketone (PEEK) Cage Device and Local Autograft Bone
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 2
• A Real Welcome Home: Permanent Housing for Homeless Veterans
• Veterans’ Satisfaction With Erectile Dysfunction Treatment
• VA PBM Academic Detailing Service: Implementation and Lessons Learned
• Adherence to Disease-Modifying Therapies in Patients With MS: A Retrospective Cohort Study
• The Role of Fidaxomicin in Clostridium difficile Infection

Click here to access the May 2016 Digital Edition. 

Table of Contents

• Why VA Health Care Is Different
• Anterior Cervical Interbody Fusion Using Polyetheretherketone (PEEK) Cage Device and Local Autograft Bone
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 2
• A Real Welcome Home: Permanent Housing for Homeless Veterans
• Veterans’ Satisfaction With Erectile Dysfunction Treatment
• VA PBM Academic Detailing Service: Implementation and Lessons Learned
• Adherence to Disease-Modifying Therapies in Patients With MS: A Retrospective Cohort Study
• The Role of Fidaxomicin in Clostridium difficile Infection

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

May has arrived, and for the majority of your patients it signals the end of the school year and the beginning of summer vacation. Zika virus is on the minds of most people since its arrival to the Western Hemisphere in March 2015. With the fluidity of this outbreak and almost daily news updates and recommendations, many parents have voiced or will be voicing concerns regarding summer travel destinations.

Many concerns about Zika virus have been previously addressed in this column (“Zika virus: More questions than answers?” by Dr. Kristina Bryant). However, if the decision is to avoid international travel because of the ongoing Zika outbreak, it doesn’t mean your patients get a free pass and will not have to be concerned about acquiring any infectious diseases. They still need to be vigilant about avoiding those pesky vectors that transmit arboviruses and other vector-borne diseases that occur in the United States.

Arboviruses are transmitted by mosquitoes, ticks, or fleas. Most infections are subclinical. If symptoms develop, they are manifested by a generalized febrile illness including fever, headache, myalgia, arthralgia, and rash. Hemorrhagic fever (dengue) or neuroinvasive disease can include aseptic meningitis, encephalitis, or acute flaccid paralysis. Neuroinvasive disease rarely occurs with dengue, Colorado tick fever, and chikungunya infections.

While more than 100 arboviruses can cause infection, some of the more common arboviruses associated with human disease include West Nile, first detected in the United States in 1999 and chikungunya, first reported in the Americas in 2013 with local transmission documented in Florida, Puerto Rico, and the U.S. Virgin Islands in 2014. It is estimated that dengue causes over 100 million cases worldwide annually. Almost 40% of the world’s inhabitants live in endemic areas. The majority of cases on the U.S. mainland are imported. However, it is endemic in all U.S. territories including Guam, American Samoa, the U.S. Virgin Islands, and Puerto Rico. Between September 2015 and March 2016, Hawaii experienced a dengue outbreak involving 264 individuals including 46 children. As of April 16, 2016, there were no infectious individuals on the island.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Other domestic arboviruses causing disease include St. Louis, Eastern, and Western Equine encephalitis, La Crosse encephalitis, Colorado tick fever, and Powassan virus. All are transmitted by mosquitoes with the exception of Powassan and Colorado tick fever, which are transmitted by ticks. The numbers of cases nationally are much lower for these diseases, compared with West Nile, dengue, and chikungunya. National and state-specific information is available for domestic arboviruses at diseasemaps.usgs.gov/mapviewer. Data is compiled by ArboNET, a national arboviral surveillance system that is managed by the Centers for Disease Control and Prevention (CDC) in conjunction with state health departments. Not only is human disease monitored, but it also maintains data on viremic blood donors, dead birds, mosquitoes, veterinary disease cases, and sentinel animals.

Spring and summer are the most active seasons for ticks. Bacterial and spirochetal diseases transmitted by them include rickettsial diseases such as Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis. Tularemia in addition to Lyme and tick-borne relapsing fever are also transmitted by ticks. Babesiosis, which is due to a parasite, and southern tick-associated rash illness (STARI), whose causative agent is yet to be determined, are two additional tick-related diagnoses.

Of note, dengue, chikungunya, and Zika are all transmitted by infected Aedes mosquitoes. There is no enzootic cycle. Just human-mosquito-human transmission. In contrast, West Nile virus is transmitted by Culex mosquitoes in an enzootic cycle between an avian reservoir and humans.

Treatment

There is no specific treatment for arboviral infections. The primary goal is relief of symptoms with fluids, bed rest, and analgesics. For bacterial vector-borne diseases, antibiotic therapy is indicated and is based on the specific pathogen. Doxycycline is the drug of choice for treatment of suspected and confirmed Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis even in children less than 8 years of age. Delay in initiation of antimicrobial therapy pending definitive diagnosis may lead to an adverse outcome. It is also the drug of choice for tick-borne relapsing fever.

Lyme disease is also responsive to antibiotic treatment. Therapy is based on the disease category. (Lyme disease in “Red Book: 2015 Report of the Committee on Infectious Diseases,” [Elk Grove Village, Ill.: American Academy of Pediatrics, 2015, pp. 516-25]).

STARI clinically presents with a lesion that resembles erythema migrans in southern and southeastern states. However, it has not been associated with any of the complications reported with disseminated Lyme disease. Treatment is not recommended.

Tularemia and babesiosis are both responsive to antimicrobial therapy and would best be managed in consultation with an infectious disease physician.

A handy, concise, up to date reference guide about all of the tick-borne diseases including photographs is available at the App Store. The Tickborne Diseases App was developed by the CDC and it is free!

Prevention

The cornerstone of disease prevention is avoidance of mosquito and tick bites, in addition to eliminating mosquito breeding sites. Ticks are generally found near the ground, in brushy or wooded areas. They usually wait for a potential host to brush against them. When this happens, they climb onto the host and find a site to attach.

Is there a role for antimicrobial prophylaxis once a tick has been discovered? There is no data to support antimicrobial prophylaxis to prevent Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis. Prophylaxis with doxycycline or ciprofloxacin is recommended for children and adults after exposure to an intentional release of tularemia and for laboratory workers after inadvertent exposure. For prevention of Lyme disease, a single dose of doxycycline (4 mg/kg, max dose 200 mg) may be offered under limited conditions: The patient is at least 8 years of age, resides in an area where Lyme is highly endemic, the tick removed was engorged, therapy can be initiated within 72 hours after tick removal, and the estimated time of attachment was at least 36 hours. There is inadequate data on the use of amoxicillin.

Remember, not all mosquitoes are alike. Those that transmit chikungunya, dengue, and Zika (Aedes mosquitoes) are primarily daytime mosquitoes, but also can bite at night. West Nile is transmitted by Culex mosquitoes, which feed from dusk to dawn.

Here are some tips to share with your patients that should decrease their chances of acquiring a mosquito or tick-borne disease:

• Apply mosquito repellent only to intact exposed skin when outdoors. Most repellents can be safely used on children at least 2 months of age and older. Avoid applying repellent directly on the child’s hand. Use at least a 20% DEET (N,N-diethyl-meta-toluamide) containing product. Other Environmental Protection Agency–registered repellents are an alternative (Additional information is available at http://www2.epa.gov/insect-repellents). Products containing oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) should not be used on children under 3 years of age.

• Apply permethrin to clothing, hats, boots, and so on. It is designed to repel mosquitoes and ticks. It can last for several washings. It is ideal to spray over nets covering carriers in children younger than 2 months of age.

• Wear long-sleeved shirts and long pants tucked inside of socks when hiking.

• Check for ticks daily, especially under the arms, behind the ears, around the waist, behind the knees, and inside belly buttons after outdoor activities.

• Have your patients learn how to effectively remove a tick. With a fine tipped tweezer, grasp the tick as close to the skin as possible and pull straight up with even pressure. Do not twist or jerk the tick. Do not squash the tick. Place it in a bag and dispose of it. Clean the site after removal with alcohol, iodine, or soap and water.

• Encourage families to mosquito proof their home by using screens on windows and doors, and using air conditioning when available.

• Empty and scrub all items that contain water such as birdbaths, planters, or wading pools around the outside of the home at least weekly because mosquitoes lay eggs in or near free standing water.

• Dogs and cats should be treated for ticks as recommended by the veterinarian.

The impact of the ongoing Zika virus outbreak is uncertain. While it may have an impact on those planning international travel now and in the near future, several arboviral and vector-borne diseases currently exist in the United States. Encouraging our patients to practice interventions to prevent mosquito and tick bites now will also serve to protect them if Zika virus becomes established in the Aedes mosquitoes here in the future and/or if they have plans for international travel. For up to date information on Zika virus for yourself and your patients, visit www.cdc.gov/zika.

Bonnie M. Word, M.D., is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email Dr. Word at [email protected].

May has arrived, and for the majority of your patients it signals the end of the school year and the beginning of summer vacation. Zika virus is on the minds of most people since its arrival to the Western Hemisphere in March 2015. With the fluidity of this outbreak and almost daily news updates and recommendations, many parents have voiced or will be voicing concerns regarding summer travel destinations.

Many concerns about Zika virus have been previously addressed in this column (“Zika virus: More questions than answers?” by Dr. Kristina Bryant). However, if the decision is to avoid international travel because of the ongoing Zika outbreak, it doesn’t mean your patients get a free pass and will not have to be concerned about acquiring any infectious diseases. They still need to be vigilant about avoiding those pesky vectors that transmit arboviruses and other vector-borne diseases that occur in the United States.

Arboviruses are transmitted by mosquitoes, ticks, or fleas. Most infections are subclinical. If symptoms develop, they are manifested by a generalized febrile illness including fever, headache, myalgia, arthralgia, and rash. Hemorrhagic fever (dengue) or neuroinvasive disease can include aseptic meningitis, encephalitis, or acute flaccid paralysis. Neuroinvasive disease rarely occurs with dengue, Colorado tick fever, and chikungunya infections.

While more than 100 arboviruses can cause infection, some of the more common arboviruses associated with human disease include West Nile, first detected in the United States in 1999 and chikungunya, first reported in the Americas in 2013 with local transmission documented in Florida, Puerto Rico, and the U.S. Virgin Islands in 2014. It is estimated that dengue causes over 100 million cases worldwide annually. Almost 40% of the world’s inhabitants live in endemic areas. The majority of cases on the U.S. mainland are imported. However, it is endemic in all U.S. territories including Guam, American Samoa, the U.S. Virgin Islands, and Puerto Rico. Between September 2015 and March 2016, Hawaii experienced a dengue outbreak involving 264 individuals including 46 children. As of April 16, 2016, there were no infectious individuals on the island.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Other domestic arboviruses causing disease include St. Louis, Eastern, and Western Equine encephalitis, La Crosse encephalitis, Colorado tick fever, and Powassan virus. All are transmitted by mosquitoes with the exception of Powassan and Colorado tick fever, which are transmitted by ticks. The numbers of cases nationally are much lower for these diseases, compared with West Nile, dengue, and chikungunya. National and state-specific information is available for domestic arboviruses at diseasemaps.usgs.gov/mapviewer. Data is compiled by ArboNET, a national arboviral surveillance system that is managed by the Centers for Disease Control and Prevention (CDC) in conjunction with state health departments. Not only is human disease monitored, but it also maintains data on viremic blood donors, dead birds, mosquitoes, veterinary disease cases, and sentinel animals.

Spring and summer are the most active seasons for ticks. Bacterial and spirochetal diseases transmitted by them include rickettsial diseases such as Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis. Tularemia in addition to Lyme and tick-borne relapsing fever are also transmitted by ticks. Babesiosis, which is due to a parasite, and southern tick-associated rash illness (STARI), whose causative agent is yet to be determined, are two additional tick-related diagnoses.

Of note, dengue, chikungunya, and Zika are all transmitted by infected Aedes mosquitoes. There is no enzootic cycle. Just human-mosquito-human transmission. In contrast, West Nile virus is transmitted by Culex mosquitoes in an enzootic cycle between an avian reservoir and humans.

Treatment

There is no specific treatment for arboviral infections. The primary goal is relief of symptoms with fluids, bed rest, and analgesics. For bacterial vector-borne diseases, antibiotic therapy is indicated and is based on the specific pathogen. Doxycycline is the drug of choice for treatment of suspected and confirmed Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis even in children less than 8 years of age. Delay in initiation of antimicrobial therapy pending definitive diagnosis may lead to an adverse outcome. It is also the drug of choice for tick-borne relapsing fever.

Lyme disease is also responsive to antibiotic treatment. Therapy is based on the disease category. (Lyme disease in “Red Book: 2015 Report of the Committee on Infectious Diseases,” [Elk Grove Village, Ill.: American Academy of Pediatrics, 2015, pp. 516-25]).

STARI clinically presents with a lesion that resembles erythema migrans in southern and southeastern states. However, it has not been associated with any of the complications reported with disseminated Lyme disease. Treatment is not recommended.

Tularemia and babesiosis are both responsive to antimicrobial therapy and would best be managed in consultation with an infectious disease physician.

A handy, concise, up to date reference guide about all of the tick-borne diseases including photographs is available at the App Store. The Tickborne Diseases App was developed by the CDC and it is free!

Prevention

The cornerstone of disease prevention is avoidance of mosquito and tick bites, in addition to eliminating mosquito breeding sites. Ticks are generally found near the ground, in brushy or wooded areas. They usually wait for a potential host to brush against them. When this happens, they climb onto the host and find a site to attach.

Is there a role for antimicrobial prophylaxis once a tick has been discovered? There is no data to support antimicrobial prophylaxis to prevent Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis. Prophylaxis with doxycycline or ciprofloxacin is recommended for children and adults after exposure to an intentional release of tularemia and for laboratory workers after inadvertent exposure. For prevention of Lyme disease, a single dose of doxycycline (4 mg/kg, max dose 200 mg) may be offered under limited conditions: The patient is at least 8 years of age, resides in an area where Lyme is highly endemic, the tick removed was engorged, therapy can be initiated within 72 hours after tick removal, and the estimated time of attachment was at least 36 hours. There is inadequate data on the use of amoxicillin.

Remember, not all mosquitoes are alike. Those that transmit chikungunya, dengue, and Zika (Aedes mosquitoes) are primarily daytime mosquitoes, but also can bite at night. West Nile is transmitted by Culex mosquitoes, which feed from dusk to dawn.

Here are some tips to share with your patients that should decrease their chances of acquiring a mosquito or tick-borne disease:

• Apply mosquito repellent only to intact exposed skin when outdoors. Most repellents can be safely used on children at least 2 months of age and older. Avoid applying repellent directly on the child’s hand. Use at least a 20% DEET (N,N-diethyl-meta-toluamide) containing product. Other Environmental Protection Agency–registered repellents are an alternative (Additional information is available at http://www2.epa.gov/insect-repellents). Products containing oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) should not be used on children under 3 years of age.

• Apply permethrin to clothing, hats, boots, and so on. It is designed to repel mosquitoes and ticks. It can last for several washings. It is ideal to spray over nets covering carriers in children younger than 2 months of age.

• Wear long-sleeved shirts and long pants tucked inside of socks when hiking.

• Check for ticks daily, especially under the arms, behind the ears, around the waist, behind the knees, and inside belly buttons after outdoor activities.

• Have your patients learn how to effectively remove a tick. With a fine tipped tweezer, grasp the tick as close to the skin as possible and pull straight up with even pressure. Do not twist or jerk the tick. Do not squash the tick. Place it in a bag and dispose of it. Clean the site after removal with alcohol, iodine, or soap and water.

• Encourage families to mosquito proof their home by using screens on windows and doors, and using air conditioning when available.

• Empty and scrub all items that contain water such as birdbaths, planters, or wading pools around the outside of the home at least weekly because mosquitoes lay eggs in or near free standing water.

• Dogs and cats should be treated for ticks as recommended by the veterinarian.

The impact of the ongoing Zika virus outbreak is uncertain. While it may have an impact on those planning international travel now and in the near future, several arboviral and vector-borne diseases currently exist in the United States. Encouraging our patients to practice interventions to prevent mosquito and tick bites now will also serve to protect them if Zika virus becomes established in the Aedes mosquitoes here in the future and/or if they have plans for international travel. For up to date information on Zika virus for yourself and your patients, visit www.cdc.gov/zika.

Bonnie M. Word, M.D., is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email Dr. Word at [email protected].

May has arrived, and for the majority of your patients it signals the end of the school year and the beginning of summer vacation. Zika virus is on the minds of most people since its arrival to the Western Hemisphere in March 2015. With the fluidity of this outbreak and almost daily news updates and recommendations, many parents have voiced or will be voicing concerns regarding summer travel destinations.

Many concerns about Zika virus have been previously addressed in this column (“Zika virus: More questions than answers?” by Dr. Kristina Bryant). However, if the decision is to avoid international travel because of the ongoing Zika outbreak, it doesn’t mean your patients get a free pass and will not have to be concerned about acquiring any infectious diseases. They still need to be vigilant about avoiding those pesky vectors that transmit arboviruses and other vector-borne diseases that occur in the United States.

Arboviruses are transmitted by mosquitoes, ticks, or fleas. Most infections are subclinical. If symptoms develop, they are manifested by a generalized febrile illness including fever, headache, myalgia, arthralgia, and rash. Hemorrhagic fever (dengue) or neuroinvasive disease can include aseptic meningitis, encephalitis, or acute flaccid paralysis. Neuroinvasive disease rarely occurs with dengue, Colorado tick fever, and chikungunya infections.

While more than 100 arboviruses can cause infection, some of the more common arboviruses associated with human disease include West Nile, first detected in the United States in 1999 and chikungunya, first reported in the Americas in 2013 with local transmission documented in Florida, Puerto Rico, and the U.S. Virgin Islands in 2014. It is estimated that dengue causes over 100 million cases worldwide annually. Almost 40% of the world’s inhabitants live in endemic areas. The majority of cases on the U.S. mainland are imported. However, it is endemic in all U.S. territories including Guam, American Samoa, the U.S. Virgin Islands, and Puerto Rico. Between September 2015 and March 2016, Hawaii experienced a dengue outbreak involving 264 individuals including 46 children. As of April 16, 2016, there were no infectious individuals on the island.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Other domestic arboviruses causing disease include St. Louis, Eastern, and Western Equine encephalitis, La Crosse encephalitis, Colorado tick fever, and Powassan virus. All are transmitted by mosquitoes with the exception of Powassan and Colorado tick fever, which are transmitted by ticks. The numbers of cases nationally are much lower for these diseases, compared with West Nile, dengue, and chikungunya. National and state-specific information is available for domestic arboviruses at diseasemaps.usgs.gov/mapviewer. Data is compiled by ArboNET, a national arboviral surveillance system that is managed by the Centers for Disease Control and Prevention (CDC) in conjunction with state health departments. Not only is human disease monitored, but it also maintains data on viremic blood donors, dead birds, mosquitoes, veterinary disease cases, and sentinel animals.

Spring and summer are the most active seasons for ticks. Bacterial and spirochetal diseases transmitted by them include rickettsial diseases such as Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis. Tularemia in addition to Lyme and tick-borne relapsing fever are also transmitted by ticks. Babesiosis, which is due to a parasite, and southern tick-associated rash illness (STARI), whose causative agent is yet to be determined, are two additional tick-related diagnoses.

Of note, dengue, chikungunya, and Zika are all transmitted by infected Aedes mosquitoes. There is no enzootic cycle. Just human-mosquito-human transmission. In contrast, West Nile virus is transmitted by Culex mosquitoes in an enzootic cycle between an avian reservoir and humans.

Treatment

There is no specific treatment for arboviral infections. The primary goal is relief of symptoms with fluids, bed rest, and analgesics. For bacterial vector-borne diseases, antibiotic therapy is indicated and is based on the specific pathogen. Doxycycline is the drug of choice for treatment of suspected and confirmed Rocky Mountain Spotted Fever, ehrlichiosis, and anaplasmosis even in children less than 8 years of age. Delay in initiation of antimicrobial therapy pending definitive diagnosis may lead to an adverse outcome. It is also the drug of choice for tick-borne relapsing fever.

Lyme disease is also responsive to antibiotic treatment. Therapy is based on the disease category. (Lyme disease in “Red Book: 2015 Report of the Committee on Infectious Diseases,” [Elk Grove Village, Ill.: American Academy of Pediatrics, 2015, pp. 516-25]).

STARI clinically presents with a lesion that resembles erythema migrans in southern and southeastern states. However, it has not been associated with any of the complications reported with disseminated Lyme disease. Treatment is not recommended.

Tularemia and babesiosis are both responsive to antimicrobial therapy and would best be managed in consultation with an infectious disease physician.

A handy, concise, up to date reference guide about all of the tick-borne diseases including photographs is available at the App Store. The Tickborne Diseases App was developed by the CDC and it is free!

Prevention

The cornerstone of disease prevention is avoidance of mosquito and tick bites, in addition to eliminating mosquito breeding sites. Ticks are generally found near the ground, in brushy or wooded areas. They usually wait for a potential host to brush against them. When this happens, they climb onto the host and find a site to attach.

Is there a role for antimicrobial prophylaxis once a tick has been discovered? There is no data to support antimicrobial prophylaxis to prevent Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis. Prophylaxis with doxycycline or ciprofloxacin is recommended for children and adults after exposure to an intentional release of tularemia and for laboratory workers after inadvertent exposure. For prevention of Lyme disease, a single dose of doxycycline (4 mg/kg, max dose 200 mg) may be offered under limited conditions: The patient is at least 8 years of age, resides in an area where Lyme is highly endemic, the tick removed was engorged, therapy can be initiated within 72 hours after tick removal, and the estimated time of attachment was at least 36 hours. There is inadequate data on the use of amoxicillin.

Remember, not all mosquitoes are alike. Those that transmit chikungunya, dengue, and Zika (Aedes mosquitoes) are primarily daytime mosquitoes, but also can bite at night. West Nile is transmitted by Culex mosquitoes, which feed from dusk to dawn.

Here are some tips to share with your patients that should decrease their chances of acquiring a mosquito or tick-borne disease:

• Apply mosquito repellent only to intact exposed skin when outdoors. Most repellents can be safely used on children at least 2 months of age and older. Avoid applying repellent directly on the child’s hand. Use at least a 20% DEET (N,N-diethyl-meta-toluamide) containing product. Other Environmental Protection Agency–registered repellents are an alternative (Additional information is available at http://www2.epa.gov/insect-repellents). Products containing oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) should not be used on children under 3 years of age.

• Apply permethrin to clothing, hats, boots, and so on. It is designed to repel mosquitoes and ticks. It can last for several washings. It is ideal to spray over nets covering carriers in children younger than 2 months of age.

• Wear long-sleeved shirts and long pants tucked inside of socks when hiking.

• Check for ticks daily, especially under the arms, behind the ears, around the waist, behind the knees, and inside belly buttons after outdoor activities.

• Have your patients learn how to effectively remove a tick. With a fine tipped tweezer, grasp the tick as close to the skin as possible and pull straight up with even pressure. Do not twist or jerk the tick. Do not squash the tick. Place it in a bag and dispose of it. Clean the site after removal with alcohol, iodine, or soap and water.

• Encourage families to mosquito proof their home by using screens on windows and doors, and using air conditioning when available.

• Empty and scrub all items that contain water such as birdbaths, planters, or wading pools around the outside of the home at least weekly because mosquitoes lay eggs in or near free standing water.

• Dogs and cats should be treated for ticks as recommended by the veterinarian.

The impact of the ongoing Zika virus outbreak is uncertain. While it may have an impact on those planning international travel now and in the near future, several arboviral and vector-borne diseases currently exist in the United States. Encouraging our patients to practice interventions to prevent mosquito and tick bites now will also serve to protect them if Zika virus becomes established in the Aedes mosquitoes here in the future and/or if they have plans for international travel. For up to date information on Zika virus for yourself and your patients, visit www.cdc.gov/zika.

Bonnie M. Word, M.D., is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email Dr. Word at [email protected].

To the Editor: I read with great interest the commentary by Lau and Naugler¹ regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)² and updated in 2016 (3rd edition) in the I/LA-20 guidance document.³

The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.⁴ Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease. 

Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion⁵ of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.

While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.^6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.

Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.^2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.

The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.⁸  These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.

Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.^9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.

Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.

To the Editor: I read with great interest the commentary by Lau and Naugler¹ regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)² and updated in 2016 (3rd edition) in the I/LA-20 guidance document.³

The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.⁴ Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease. 

Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion⁵ of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.

While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.^6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.

Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.^2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.

The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.⁸  These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.

Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.^9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.

Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.

To the Editor: I read with great interest the commentary by Lau and Naugler¹ regarding how much allergen-specific immunoglobulin E (IgE) testing is too much. The authors made a number of important conclusions that directly contradict the international consensus statement on IgE antibody test performance published by the Clinical Laboratory Standards Institute (CLSI) in 2009 (2nd edition)² and updated in 2016 (3rd edition) in the I/LA-20 guidance document.³

The most important conclusion of the CLSI I/LA-20 panel was to reaffirm the golden rule of diagnostic allergy testing, which states that allergen-specific IgE antibody detected by either skin testing or serology methods is simply a marker for sensitization and thus only one of many risk factors for allergic disease. IgE positivity is not synonymous with the presence of allergic disease without a positive clinical history.⁴ Clinicians, since the time that IgE was discovered as the reagin in 1967, have tried to use the presence of IgE antibody as detected either by skin testing or serology as the definitive indicator of allergic disease. This is simply inappropriate. Both skin testing and serology are diagnostic tests that indicate sensitization (the presence of IgE antibody) and not disease. The clinician using a positive clinical history of allergic symptoms, objectively collected, must make the link between sensitization (IgE antibody positivity) and allergic disease. 

Lau and Naugler make this same mistake and conclude from their Figure 1 data that “serum antigen-specific IgE testing is not a reliable diagnostic tool.” They use the Wians criterion⁵ of the summed diagnostic sensitivity and specificity of 170 to indicate if a test is clinically useful. They determined the sums of the diagnostic sensitivity and specificity for 89 allergen specificities, most of which they report as below 170. Among the specificities they cover are select aeroallergens, food allergens, venoms, and drugs. Importantly, they use a positive threshold of 0.35 kU/L for only some of their specificities, and they consider a sum of the diagnostic sensitivity and specificity equal to or greater than 170 as clinically relevant.

While Wians’ analysis may have been appropriate for laboratory tests like glucose and even prostate-specific antigen that associate closely with defining a disease state, this criterion is inappropriate for IgE antibody tests that do not directly identify allergic disease. There is peer-reviewed literature on nonreactors based on their clinical history with a validated positive IgE skin test, IgE antibody serology, or food challenge tests.^6,7 Thus, the data in their Figure 1 have no value in defining the performance of IgE antibody tests of sensitization.

Moreover, their report is vague on the actual IgE antibody assay method that was used. This information is important because we know that different IgE assay methods measure different populations of IgE antibody.^2,3 Also, the report does not define whether the participants who provided sera for testing actually had physician-defined allergic disease based on an objective clinical history.

The act of determining optimal cutoff values to maximize the “diagnostic” sensitivity and specificity is appropriate for many laboratory tests, but for allergen-specific IgE antibody analyses, it should be considered inappropriate. These are tests of sensitization, not disease. The IgE antibody result should be reported down to the regulatory-cleared and manufacturer-defined analytical sensitivity, which for the principal IgE antibody autoanalyzers used worldwide is 0.1 kU/L.⁸  These concerns essentially invalidate the conclusions of their report. Unfortunately, they leave the reader with misleading negative impressions about the utility of IgE antibody analyses that are extensively validated methods.

Finally, contrary to the assertions of the authors, current commentaries on the topic of relative diagnostic performance of skin testing and autoanalyzer-based IgE serology tests support the conclusion that, especially for aeroallergens, both the in vivo skin test and the current autoanalyzer-based in vitro serology tests provide overlapping, indistinguishable, and thus comparable diagnostic sensitivity and specificity results.^9,10 Unfortunately, the authors refer to the 2008 Bernstein practice parameter that is out of date in relation to autoanalyzer technology, which has advanced by 2016.

Thus, contrary to the assertions of Lau and Naugler, IgE antibody serology has a clear, well-defined, and positive role in defining sensitization as a key part of the diagnostic workup of a patient who is suspected of having allergic disease. As with any laboratory test, IgE antibody measurements need to be judiciously ordered and used by the clinician only when there is a strong pretest likelihood, based on the patient’s clinical history, of allergic disease.

In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.

There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.

It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.

In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references. 

In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.

There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.

It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.

In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references. 

In Reply: We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript.

There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum IgE testing should not be used as the sole diagnostic tool because it is an indicator of sensitization, not disease, and that clinical history should always be used in conjunction to ensure proper diagnosis.

It is our experience that some clinicians indiscriminately order large panels of serum IgE tests. As Dr. Hamilton indicates, patients can have positive serum IgE results but not display allergy symptoms, which can lead to unnecessary food avoidance. In addition, false-negative results from injudiciously ordered tests (ie, not based on pretest probability) can lead to missed diagnoses. All of these points should be kept in mind in delivering good clinical care, and as such, Choosing Wisely has highlighted the importance of using this test appropriately.

In response to the origin of the sensitivities and specificities used to calculate the sum, the values were curated from available literature and thus limited the number of allergens that could be profiled. A cutoff of 0.35 kU/L was used because this was the cutoff used by the references.